ascorbic-acid and Stomach-Neoplasms

Topics: Animals; Antioxidants; Ascorbic Acid; Carcinogenesis; Gastric Juice; Helicobacter Infections; Helicobacter pylori; Humans; Phytochemicals; Stomach Neoplasms

China has some of the highest incidence rates for gastric adenocarcinoma (GA) and esophageal squamous cell carcinoma (ESCC) in the world. Prospective studies suggested that vitamin C may reduce risks; however, associations are unclear because of limited sample size.. The objective was to examine the relation between prediagnostic plasma vitamin C and the risk of GA and ESCC.. A case-cohort study was used to assess the association between prediagnostic plasma vitamin C and incidence of GA (n = 467) and ESCC (n = 618) in the General Population Nutrition Intervention Trial. With the use of multivariate Cox proportional hazards models, we estimated the HRs and 95% CIs. We also conducted a meta-analysis of the literature up to 1 October 2012 on the relation between circulating vitamin C and gastric cancer incidence. Two cohort studies and the current study were included to assess the body of evidence.. For GA, each 20-μmol/L increase in plasma vitamin C was associated with a 14% decrease in risk (HR: 0.86; 95% CI: 0.76, 0.96). Compared with individuals with low plasma vitamin C concentrations (≤28 μmol/L), those with normal concentrations (>28 μmol/L) had a 27% reduced risk of GA (HR: 0.73; 95% CI: 0.56, 0.94). No association between vitamin C concentrations and ESCC was seen. Meta-analysis showed that the risk of incident GA among those with the highest concentration of plasma vitamin C was 31% lower (random-effects-pooled-odds ratio 0.69; 95% CI: 0.54, 0.89) than those in the lowest category.. Our data provide evidence that higher circulating vitamin C was associated with a reduced risk of incident GA, but no association was seen for ESCC.

Topics: Ascorbic Acid; Asian People; Carcinoma, Squamous Cell; China; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Incidence; Odds Ratio; Proportional Hazards Models; Prospective Studies; Risk Factors; Stomach Neoplasms

Gastric cancer (GC) is the result of a long multi-step and multifactorial process involving possible interactions between Helicobacter pylori infection, environmental exposures and host genetic susceptibility. Interactions between H. pylori infection, tobacco smoking and dietary antioxidants are biologically plausible. Positive interactions between risk factors imply that, in certain subgroups of the population, the risk of GC associated with simultaneous exposure to these factors is higher than that in the rest of the population, and these subgroups have to be the target for preventive measures. Using PubMed, we reviewed all studies published in English up to December 2008 carried out in humans on interactions between H. pylori infection and smoking exposure and between H. pylori infection and dietary factors in gastric carcinogenesis. Although relatively few epidemiological studies have evaluated the effect of the interaction between smoking and H. pylori infection on GC risk, there is a suggestion of a positive interaction between the two factors. In contrast, evidence suggests a negative interaction between dietary antioxidants and H. pylori infections on GC risk. The potential protective effect of dietary antioxidants such as vitamins C and E and beta-carotene seems to be stronger in those infected by H. pylori, even though results are inconsistent. In Asian populations, subjects infected by H. pylori and with high dietary salt intake may have a higher risk of GC than subjects without H. pylori infection and with a low salt intake. The risk of GC associated with red meat, processed meat or endogenous formation of nitrosamines appears to only be observed in subjects infected by H. pylori. More and larger epidemiological studies, mainly prospective studies, are necessary to reach a more definitive conclusion on these interactions.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Diet; Environmental Exposure; Helicobacter Infections; Humans; Risk Factors; Smoking; Stomach Neoplasms; Vitamin E

Data from epidemiologic, experimental, and animal studies indicate that diet plays an important role in the etiology of gastric cancer. High intake of fresh fruits and vegetables, lycopene and lycopene-containing food products, and potentially vitamin C and selenium may reduce the risk for gastric cancer. Data also suggest that high intake of nitrosamines, processed meat products, salt and salted foods, and overweight and obesity are associated with increased risk for gastric cancer. However, current data provide little support for an association of beta-carotene, vitamin E, and alcohol consumption with risk for gastric cancer.

Topics: Animals; Antioxidants; Ascorbic Acid; Carotenoids; Diet; Fruit; Humans; Nitrates; Nutritional Physiological Phenomena; Risk Factors; Selenium; Stomach Neoplasms; Vegetables; Vitamin E

Topics: Animals; Ascorbic Acid; Esophageal Neoplasms; Esophagogastric Junction; Gastric Acid; Humans; Nitrates; Nitric Oxide; Nitrous Acid; Stomach Neoplasms

Ascorbic acid, as one of the important water-soluble vitamins, is essential for a range of physiological functions, including the syntheses of collagen, carnitine and neurotransmitters. It is also an important dietary antioxidant against oxidative stress. Current information suggests that vitamin C might be protective against the development of gastric cancer. Chronic infection with Helicobacter pylori is recognized to be a significant cause of gastric adenocarcinoma. Inflammation induced by H. pylori infection in the stomach not only causes significantly enhanced consumption of vitamin C, but also reduces secretion of the vitamin into the gastric lumen. Most of the evidence relating to vitamin C and H. pylori infection derives from clinical studies and experiments directly examining the effect of vitamin C on H. pylori-associated gastric carcinogenesis and remains limited. Furthermore, results from recent studies suggest that vitamin C might also increase the risk of cancer through its pro-oxidant activity and protect against oxidative stress in cancer cells through its antioxidant action. In this article we review recent publications on vitamin C research and assess the potential roles of vitamin C in H. pylori associated gastric carcinogenesis. The possible adverse effects of the vitamin C are also discussed.

Topics: Adenocarcinoma; Animals; Antioxidants; Ascorbic Acid; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Oxidative Stress; Risk Factors; Stomach Neoplasms; T-Lymphocytes

Topics: Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; Gastritis, Atrophic; Helicobacter Infections; Humans; Precancerous Conditions; Stomach; Stomach Neoplasms

Intestinal metaplasia (IM) of the stomach is a risk factor in developing intestinal-type gastric cancer and hence the question of reversibility is vital. There is emerging epidemiological evidence that with long term follow up, IM may be reversible although a combination of antioxidant agents and eradication of H pylori may be necessary to achieve this. The pathogenesis of IM is currently being elucidated and it is likely that a combination of bacterial, host, and environmental factors will be shown to lead to IM. In assessing gastric cancer risk, histochemical typing of IM will most probably be replaced by molecular markers.

Topics: Alleles; Anti-Bacterial Agents; Ascorbic Acid; CDX2 Transcription Factor; Helicobacter Infections; Helicobacter pylori; Homeodomain Proteins; Humans; Intestines; Metaplasia; Microsatellite Repeats; Precancerous Conditions; Risk; Smoking; Stomach; Stomach Neoplasms; Trans-Activators

Antioxidants are substances capable of inhibiting oxidation. In chronic diseases, inflammatory response cells produce oxygen free radicals. Oxygen free radicals cause DNA damage, and this may lead to gene modifications that might be carcinogenic. Chronic Helicobacter pylori infection causes the production of DNA-damaging free radicals. In recent years, various groups have studied the effects of antioxidants, especially on H. pylori-associated gastric cancer. In most of the studies, it has been shown that H. pylori infection does affect the level of antioxidants measured in the gastric juice, but there are also controversial results. Recent experimental studies, both in vivo and in vitro, have shown that vitamin C and astaxanthin, a carotenoid, are not only free radical scavengers but also show antimicrobial activity against H. pylori. It has been shown that astaxanthin changes the immune response to H. pylori by shifting the Th1 response towards a Th2 T-cell response. Very few experimental studies support the epidemiologic studies, and further studies are needed to describe the effect and the mechanism of antioxidants in the H. pylori immune response.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; DNA Damage; Helicobacter Infections; Helicobacter pylori; Humans; Risk Factors; Stomach Neoplasms; Th1 Cells; Th2 Cells; Xanthophylls

Vitamin C's role in the prevention of disease and malignancy has been studied over the last several decades. Vitamin C intake has been shown to have an inverse relationship with gastric cancer. Recent follow-up studies on high-risk populations suggest that ascorbic acid, the reduced form of vitamin C, protects against gastric cancer, for which H. pylori is a significant risk factor. In populations infected with H. pylori, there is a reduction in gastric juice ascorbic acid concentration. This article reviews the risk factors for gastric cancer and the role of vitamin C in prevention of the disease.

Topics: Ascorbic Acid; Disease Progression; Free Radical Scavengers; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Risk Factors; Stomach Neoplasms

Topics: Alcoholic Beverages; Animals; Antioxidants; Ascorbic Acid; Capsicum; Diet; Dietary Carbohydrates; Fruit; Humans; Nitroso Compounds; Plants, Medicinal; Risk Factors; Smoking; Sodium, Dietary; Stomach Neoplasms; Tea; Vegetables; Vitamin E

Topics: Antioxidants; Ascorbic Acid; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Lymphocytes; Stomach Neoplasms

Topics: Anticarcinogenic Agents; Ascorbic Acid; Gastric Juice; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Neoplasms

A review of the literature reveals a very consistent association between gastric cancer risk and low intake of fruits and vegetables. This observation has been documented in many countries with different epidemiological techniques: interpopulation correlations, case-control studies and follow up of several cohorts. Low serum levels of beta-carotene and alpha-tocopherol, but not vitamin C, have been reported in patients with gastric dysplasia. Helicobacter pylori infection has been associated with lower concentrations of vitamin C in the gastric juice. Detailed studies in Colombia and New Orleans have shown a gradient towards lower concentration in the gastric juice and lower ratios of gastric juice to serum concentration of vitamin C in the following comparisons: i) lower vs. higher gastric cancer risk; ii) mild vs. advanced gastric precancerous histopathologic lesions; iii) mild vs. advanced degree of atrophy; iv) mild vs. advanced damage to the surface gastric epithelium; v) lower vs. higher gastric pH. Such a gradient is not observed for serum levels of vitamin C. The role of infection with H. pylori in the metabolism of ascorbic acid is discussed, as well as the possible role of ascorbic acid in inhibiting cell damage by reactive oxygen species.

Topics: Antioxidants; Ascorbic Acid; Diet; Fruit; Gastric Juice; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Incidence; Stomach Neoplasms; Vegetables

Helicobacter pylori infection is now recognized to be an important acquired factor in the pathogenesis of duodenal ulcer disease. There is also an association between H pylori and the subsequent development of gastric cancer. The mechanism of the association between the infection and those disorders is incompletely understood but there is increasing evidence that H pylori-induced disturbances of gastric function play a pivotal role. In this article we review the role of H pylori infection in the pathophysiology of these important upper gastrointestinal diseases.

Topics: Ascorbic Acid; Duodenal Ulcer; Gastric Acid; Gastrins; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Neoplasms

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Breast Neoplasms; Case-Control Studies; Cohort Studies; Colonic Neoplasms; Diet; Dietary Fats; Ethanol; Female; Fruit; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Rectal Neoplasms; Risk Factors; Smoking; Stomach Neoplasms; Vegetables; Vitamin E

Topics: Ascorbic Acid; Cell Division; Cell Transformation, Neoplastic; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Stomach; Stomach Neoplasms

Epidemiologic evidence on the relation between nutrition and stomach cancer is reviewed. Stomach cancer shows a distinct international variation and dramatic worldwide decline. These descriptive features suggest that dietary factors are important in determining the risk of stomach cancer. The authors assessed relevant data regarding specific dietary hypotheses in the etiology of stomach cancer. A negative association with fresh vegetables and fruits is highly consistent in numerous case-control studies in different populations. Both epidemiologic and experimental data suggest that vitamins C and carotenoids lower risk of stomach cancer. Evidence is sparse and inconsistent as to protective effects of vitamin E and selenium. Epidemiologic studies have not lent, and will not provide, supportive evidence for an etiologic role of nitrate intake. High salt intake has been associated with an increased risk in many case-control studies and limited cohort studies. Taken together with animal data, it is considered that high salt intake is a risk factor for stomach cancer. Both epidemiologic and experimental data are inconclusive as to whether high-starch diets confer an increased risk. Cohort studies using quantitative dietary assessment and biologic measurement of micronutrients are needed for further understanding of etiologic roles of dietary factors in the causation of stomach cancer.

Topics: Animals; Ascorbic Acid; Carotenoids; Case-Control Studies; Causality; Cohort Studies; Diet; Fruit; Humans; Nitrates; Nutrition Assessment; Nutritional Physiological Phenomena; Risk Factors; Selenium; Sodium Chloride, Dietary; Starch; Stomach Neoplasms; Vegetables; Vitamin E

In many Western developed countries, the incidence of stomach cancer has declined dramatically. This decrease was an extraordinary, "unplanned triumph", especially when compared to other cancers. Stomach cancer is still the most prevalent malignant tumor in Korea. Most Koreans carry Helicobacter pylori in their stomach. Thus, a new hypothesis, based on the relationship between the host and Helicobacter pylori, is presented as the carcinogenesis of human stomach cancer. The reasons for why the N-nitrosamide hypothesis should be dismissed as the etiology of stomach cancer, and why the contemporarily available principles and practice of intervention strategies to rapidly decrease the surprisingly high prevalence rate of Helicobacter pylori infection are impractical at this moment, are explained. In order to introduce an alternative provisional strategy of the "planned triumph" for the population vulnerable to stomach cancer, vitamin C is defined as an anti-inflammatory agent on the basis of the pathogenesis of Helicobacter pylori infection.

Topics: Animals; Ascorbic Acid; Helicobacter Infections; Helicobacter pylori; Humans; Nitroso Compounds; Stomach Neoplasms

Topics: Ascorbic Acid; Gastric Mucosa; Humans; Nitroso Compounds; Reactive Oxygen Species; Stomach Neoplasms

Topics: Ascorbic Acid; Diet; Fruit; Humans; Nitrosation; Nitroso Compounds; Stomach Neoplasms; Vitamin E

A literature review was made to critically evaluate the ability of ascorbic acid to modulate the incidence of gastrointestinal cancer. A comparison of preclinical, clinical, and epidemiological studies indicated that evidence for ascorbic acid as an inhibitor of carcinogenesis is stronger with regard to gastric cancer and weaker with regard to esophageal and colon/rectal cancer. Insufficient evidence currently exists regarding the oral cavity and the use of ascorbic acid in precancerous conditions such as polyposis and leukoplakia.

Topics: Animals; Anticarcinogenic Agents; Ascorbic Acid; Colonic Neoplasms; Esophageal Neoplasms; Gastrointestinal Neoplasms; Humans; Rectal Neoplasms; Stomach Neoplasms

Topics: Ascorbic Acid; Duodenal Ulcer; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Stomach Neoplasms; Virulence

Ascorbic acid (ASC) consumption is negatively correlated with the incidence of certain cancers. This is a review and update of the theory, which has recently been neglected, that this negative correlation is due to ASC inhibition of in vivo nitrosation. The review covers the older literature on ASC inhibition of carcinogenesis by nitrite administered with amines or amides and more recent studies on ASC inhibition of nitrosation by bacteria, nitrogen oxides, and activated macrophages; the role of oxygen in ASC inhibition of gastric nitrosation; ASC inhibition of N-nitrosoproline formation in subjects from areas with high incidences of certain cancers; dose and temporal relationships between ASC and in vivo nitrosation in humans; the role of substances other than ASC in the inhibition of nitrosation by vegetables and fruits; and the active secretion of ASC into the human stomach.

Topics: Animals; Ascorbic Acid; Biotransformation; Diet; Fruit; Incidence; Neoplasms; Nitroso Compounds; Stomach Neoplasms; Vegetables

Humans are exposed through ingestion or inhalation to preformed N-nitroso compounds (NOC) in the environment and through the endogenous nitrosation of amino precursors in the body. Activated macrophages and bacterial strains isolated from human infections can enzymatically produce nitrosating agents and NOC from precursors at neutral pH. As a consequence, endogenous nitrosation may occur at various sites of the body, such as the oral cavity, stomach, urinary bladder, and at other sites of infection or inflammation. Numerous substances to which humans are exposed have been identified and shown to inhibit formation of NOC. Such inhibitors include vitamins C and E, certain phenolic compounds, and complex mixtures such as fruit and vegetable juices or other plant extracts. Nitrosation inhibitors normally destroy the nitrosating agents and, thus, act as competitors for the amino compound that serves as substrate for the nitrosating species. Independently, epidemiological studies have already established that fresh fruits and vegetables that are sources of vitamin C, other vitamins, and polyphenols have a protective effect against cancers at various sites and in particular gastric cancer. This article briefly reviews (a) the chemistry of NOC formation and inhibition; (b) the studies in experimental animals that showed that inhibition of endogenous NOC synthesis leads to a reduction of toxic, mutagenic, and carcinogenic effects; (c) recent studies in humans where the degree of inhibition of endogenous NOC synthesis was directly quantified; and (d) the possible contribution of nitrosation inhibitors to human cancer prevention.

Topics: Animals; Antimutagenic Agents; Ascorbic Acid; Cholangiocarcinoma; Esophageal Neoplasms; Humans; Incidence; Infant, Newborn; Macrophage Activation; Macrophages; Neoplasms; Nitroso Compounds; Opisthorchiasis; Phenols; Risk Factors; Stomach Neoplasms; Vitamin E

Topics: Antacids; Anti-Ulcer Agents; Ascorbic Acid; Gastric Acid; Gastric Juice; Helicobacter Infections; Helicobacter pylori; Humans; Intestine, Small; Risk Factors; Stomach; Stomach Neoplasms

Evidence from pathology and epidemiology studies has been provided for a human model of gastric carcinogenesis with the following sequential stages: chronic gastritis; atrophy; intestinal metaplasia; and dysplasia. The initial stages of gastritis and atrophy have been linked to excessive salt intake and infection with Helicobacter pylori. The intermediate stages have been associated with the ingestion of ascorbic acid and nitrate, determinants of intragastric nitrosation. The final stages have been linked with the supply of beta-carotene and with excessive salt intake. Nitrosating agents are candidate carcinogens and could originate in the gastric cavity or in the inflammatory infiltrate.

Topics: Ascorbic Acid; Carcinogens; Gastric Mucosa; Helicobacter pylori; Humans; Sodium, Dietary; Stomach Neoplasms

Approximately 90 epidemiologic studies have examined the role of vitamin C or vitamin-C-rich foods in cancer prevention, and the vast majority have found statistically significant protective effects. Evidence is strong for cancers of the esophagus, oral cavity, stomach, and pancreas. There is also substantial evidence of a protective effect in cancers of the cervix, rectum, and breast. Even in lung cancer, for which carotenoids show a consistent protective effect, there is recent evidence of a role for vitamin C. Vitamin C is an important antioxidant and free radical scavenger in plasma and acts to regenerate active vitamin E in lipid membranes. Although several different factors in fruits and vegetables probably act jointly, the epidemiologic and biochemical evidence indicate an important role for vitamin C.

Topics: Ascorbic Acid; Epidemiologic Methods; Female; Gastrointestinal Neoplasms; Humans; Lung Neoplasms; Neoplasms; Stomach Neoplasms; Urogenital Neoplasms; Uterine Neoplasms

N-nitroso compounds (NOC) are strongly implicated in the causation of cancer of the stomach and it has been suggested that ascorbic acid might reduce the risk of gastric cancer by preventing their formation within gastric juice. However, until recently there have been no measurements of gastric juice ascorbic acid concentrations. We have measured both gastric juice ascorbic and total vitamin C (ascorbic acid and dehydroascorbic acid). Our findings suggest that ascorbic acid is secreted into the gastric lumen so that gastric juice concentrations are often greater than those in plasma. Gastric pathology affects this secretion, leading to values in gastric juice that are lower than plasma levels. Stimulation of gastric secretion does not raise vitamin C concentrations in individuals whose values are initially low. The role of ascorbic acid in preventing formation of NOC and protecting against gastric cancer is discussed in the light of these findings.

Topics: Ascorbic Acid; Gastric Juice; Humans; Nitroso Compounds; Stomach Neoplasms

The gastric formation of N-nitroso compounds probably constitutes a major source of human exposure to this important class of environmental carcinogens. Following reduction of nitrate to nitrite by oral or gastric bacteria, reaction with nitrogenous constituents of gastric juice can occur leading to the in situ formation of N-nitroso compounds, probably primarily derived from amides, ureas or aromatic amines. While gastric nitrite concentrations are raised in the achlorhydric relative to the normal stomach, the latter, owing to its acidity, offers a particularly favourable environment for the formation of N-nitroso compounds, as indicated by the finding of greatly increased gastric concentrations of N-nitroso compounds following an oral dose of nitrate. This illustrates the importance of the dynamic nature of the relationships between the various parameters involved in the formation of N-nitroso compounds. While in principle the same is true of the process of inhibition of nitrosation by reducing agents such as ascorbic acid (since, depending on the relative concentrations of reducing agent, nitrite and oxygen, inhibition or catalysis of nitrosation can occur), ingestion of 1 g ascorbic acid brings about a significant reduction in the gastric concentration of N-nitroso compounds.

Topics: Animals; Ascorbic Acid; Dose-Response Relationship, Drug; Gastric Juice; Humans; Hydrogen-Ion Concentration; Kinetics; Nitrosation; Nitroso Compounds; Oxygen; Stomach Neoplasms; Time Factors

Topics: Animals; Antioxidants; Ascorbic Acid; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Carcinogens; Colonic Neoplasms; Ethoxyquin; Glutathione Transferase; Mammary Neoplasms, Experimental; Methylnitronitrosoguanidine; Neoplasms, Experimental; Phenobarbital; Propyl Gallate; Rats; Rats, Inbred F344; Saccharin; Stomach Neoplasms; Substrate Specificity; Urinary Bladder Neoplasms

Carcinogenicity tests showed that addition of the antioxidant BHA to the diet of F344 rats induced high incidences of papilloma and squamous cell carcinoma of the forestomach of both sexes. Male hamsters given BHA for 24 weeks also developed papilloma showing downward growth into the submucosa of the forestomach. These results indicate that BHA should be classified in the category of "sufficient evidence of carcinogenicity" as judged by IARC criteria. The 3-tert isomer of BHA seemed to be responsible for the carcinogenicity of crude BHA in the forestomach of rats. BHT was not found to be carcinogenic in rats or mice. In two-stage carcinogenesis in rats after appropriate initiation, BHA enhanced carcinogenesis in the forestomach and urinary bladder of rats, but inhibited carcinogenesis in the liver. BHT enhanced the induction of urinary bladder tumors and inhibited that of liver tumors, but had no effect on carcinogenesis in the forestomach. BHT could be a promoter of thyroid carcinogenesis. Sodium L-ascorbate enhanced forestomach and urinary bladder carcinogenesis. Ethoxyquin enhanced kidney and urinary bladder carcinogenesis, but inhibited liver carcinogenesis. Thus, these antioxidants modify two-stage chemical carcinogenesis in the forestomach, liver, kidney, urinary bladder, and thyroid, but show organ-specific differences in effects.

Topics: Animals; Anisoles; Antioxidants; Ascorbic Acid; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Cocarcinogenesis; Drug Synergism; Humans; Kidney Neoplasms; Liver Neoplasms; Methylnitrosourea; Neoplasms; Species Specificity; Stomach Neoplasms; Urinary Bladder Neoplasms

Topics: Alcohol Drinking; Animals; Ascorbic Acid; Cerebrovascular Disorders; Colonic Neoplasms; Diet; Esophageal Neoplasms; Female; Fishes; Food Preservation; Food Preservatives; Humans; Hypertension; Male; Nitrites; Risk; Smoking; Stomach Neoplasms

Gastrointestinal cancers, mainly oesophageal, gastric, pancreatic and large bowel cancer, account for about 40,000 deaths annually in England and Wales which is 32% of all cancer deaths. Nutritional factors have been implicated in the cause of each cancer and probably act by promoting the effect of carcinogenic substances taken in the diet or produced in the gut. Gastric cancer for example may be due to nitrosamine production in the stomach. This is enhanced by readily available sources of dietary nitrite and nitrate whilst the reaction is inhibited by vitamin C and low temperatures (2 degrees C). By contrast large bowel cancer can be related to high fat and meat intakes whilst a protective role for dietary fibre has been suggested. Dietary factors in the aetiology of oesophageal cancer differ from one high incidence area to another.

Topics: Animals; Ascorbic Acid; Cold Temperature; Diet; Dietary Fats; Dietary Fiber; Digestive System; Esophageal Neoplasms; Gastrointestinal Motility; Gastrointestinal Neoplasms; Humans; Intestinal Neoplasms; Meat; Nitrosamines; Organ Specificity; Pancreatic Neoplasms; Stomach Neoplasms

Topics: Adenocarcinoma, Scirrhous; Adult; Amino Acids; Animals; Ascorbic Acid; Cattle; Child; Collagen; Collagen Diseases; Female; Humans; Hydroxyproline; Lung; Marfan Syndrome; Mice; Procollagen-Proline Dioxygenase; Skin Diseases; Stomach Neoplasms

Preclinical studies suggest synergistic effectiveness of ascorbic acid (AA, vitamin C) and cytotoxic agents in gastrointestinal malignancies. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AA combined with mFOLFOX6 or FOLFIRI regimens in patients with metastatic colorectal cancer (mCRC) or gastric cancer (mGC).. In the dose-escalation phase, patients received AA (0.2-1.5 g/kg, 3-h infusion, once daily, days 1-3) with mFOLFOX6 or FOLFIRI in a 14-day cycle until the MTD was reached. In the speed-expansion phase, AA was administered at the MTD or at 1.5 g/kg if the MTD was not reached at a fixed rate of 0.6, 0.8 or 1 g/min. Pharmacokinetics and preliminary efficacy were also assessed.. Thirty-six patients were enrolled. The MTD was not reached. The RP2D was established as AA at 1.5 g/kg/day, days 1-3, with mFOLFOX6 or FOLFIRI. No dose-limiting toxicity (DLT) was detected during dose escalation. The most common treatment-emergent adverse events (TRAEs) were sensory neuropathy (50%), nausea (38.9%), vomiting (36.1%) and neutropenia (27.8%). Grade 3-4 TRAEs were neutropenia (13.9%), sensory neuropathy (2.8%), vomiting (2.8%), diarrhea (2.8%) and leukopenia (2.8%). AA exposure was dose-proportional. The objective response rate was 58.3%, and the disease control rate was 95.8%. No difference in efficacy was found between mCRC patients with wild-type RAS/BRAF and mutant RAS or BRAF.. The favorable safety profile and preliminary efficacy of AA plus mFOLFOX6/FOLFIRI support further evaluation of this combination in mCRC or mGC.. ClinicalTrial.gov Identifier: NCT02969681 .

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Asian People; Colorectal Neoplasms; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Stomach Neoplasms

Evidence has shown that both C-reactive protein (CRP) and serum amyloid component A (SAA) are increased in individuals with gastritis and stomach cancer. Controlling the level of these biomarkers by inhibiting the gastric infection with high doses of ascorbic acid may reduce the risk of carcinogenesis. A population-based double-blind randomised controlled trial in a Japanese population with atrophic gastritis in an area of high stomach cancer incidence was conducted between 1995 and 2000. Daily doses of 50 or 500 mg vitamin C were given, and 120 and 124 participants completed the 5-year study, respectively. Although serum ascorbic acid was higher in the high-dosage group (1.73 (SD 0.46) μg/l) than in the low-dosage group (1.49 (SD 0.29) μg/l, P< 0.001), at the end of the study, no significant difference was observed for CRP between the low- and high-dosage groups (0.39 (95 % CI 0.04, 4.19) mg/l and 0.38 (95 % CI 0.03, 4.31) mg/l, respectively; P= 0.63) or for SAA between the low- and high-dosage groups (3.94 (95 % CI 1.04, 14.84) μg/ml and 3.85 (95 % CI 0.99, 14.92) μg/ml, respectively; P= 0.61). Vitamin C supplementation may not have a strong effect on reducing infections in individuals with atrophic gastritis.

Topics: Adult; Aged; Ascorbic Acid; C-Reactive Protein; Dietary Supplements; Double-Blind Method; Female; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Japan; Male; Middle Aged; Serum Amyloid A Protein; Stomach Neoplasms

In the Shandong Intervention Trial, 2 weeks of antibiotic treatment for Helicobacter pylori reduced the prevalence of precancerous gastric lesions, whereas 7.3 years of oral supplementation with garlic extract and oil (garlic treatment) or vitamin C, vitamin E, and selenium (vitamin treatment) did not. Here we report 14.7-year follow-up for gastric cancer incidence and cause-specific mortality among 3365 randomly assigned subjects in this masked factorial placebo-controlled trial. Conditional logistic regression was used to estimate the odds of gastric cancer incidence, and the Cox proportional hazards model was used to estimate the relative hazard of cause-specific mortality. All statistical tests were two-sided. Gastric cancer was diagnosed in 3.0% of subjects who received H pylori treatment and in 4.6% of those who received placebo (odds ratio = 0.61, 95% confidence interval = 0.38 to 0.96, P = .032). Gastric cancer deaths occurred among 1.5% of subjects assigned H pylori treatment and among 2.1% of those assigned placebo (hazard ratio [HR] of death = 0.67, 95% CI = 0.36 to 1.28). Garlic and vitamin treatments were associated with non-statistically significant reductions in gastric cancer incidence and mortality. Vitamin treatment was associated with statistically significantly fewer deaths from gastric or esophageal cancer, a secondary endpoint (HR = 0.51, 95% CI = 0.30 to 0.87; P = .014).

Topics: Adult; Aged; Amoxicillin; Anti-Bacterial Agents; Ascorbic Acid; China; Confounding Factors, Epidemiologic; Dietary Supplements; Factor Analysis, Statistical; Female; Follow-Up Studies; Garlic; Gastrointestinal Agents; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Logistic Models; Male; Middle Aged; Odds Ratio; Omeprazole; Precancerous Conditions; Proportional Hazards Models; Stomach Neoplasms; Vitamin E; Vitamins

Manganese superoxide dismutase is the primary antioxidant enzyme in the mitochondria and is involved in carcinogenesis. To investigate the association between MnSOD Val(16)Ala polymorphism and risk of advanced gastric lesions, and its effects on chemoprevention, a population-based study was conducted in Linqu, a high-risk area of gastric cancer in China.. Genotypes were determined by PCR-RFLP analysis in 3,355 subjects with the baseline histopathologic diagnosis in 1994, and 2,758 of these subjects received subsequent three interventions including vitamin supplementation for 7.3 years. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression model.. We found an increased risk of dysplasia in subjects with the Val/Ala+Ala/Ala genotype (OR, 1.31; 95% CI, 1.02-1.68) compared with the Val/Val genotype. Stratified analysis indicated that a significantly elevated risk of intestinal metaplasia (OR, 3.40; 95% CI, 2.64-4.38) or dysplasia (OR, 4.01; 95% CI, 2.79-5.74) was found in subjects carrying the Val/Ala+Ala/Ala genotype and Helicobacter pylori infection, and an interaction between this genotype and a high serum H. pylori IgG titer (>2.94) on the risk of dysplasia was observed (P(interaction) = 0.01). Furthermore, an elevated chance for regression of gastric lesions was observed in subjects with the Val/Ala+Ala/Ala genotype and high IgG titer in an intervention trial with vitamin supplementation (OR, 2.45; 95% CI, 1.37-4.38).. These findings suggest that Val(16)Ala polymorphism may play an important role in development of advanced gastric lesions and modify the effect of vitamin supplementation on the evolution of gastric lesions.. Val(16)Ala polymorphism is related to gastric cancer development.

Topics: Adult; Ascorbic Acid; Asian People; Dietary Supplements; Female; Garlic; Genetic Predisposition to Disease; Helicobacter Infections; Humans; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Precancerous Conditions; Selenium; Stomach Neoplasms; Superoxide Dismutase; Vitamin E; Vitamins

Gastric cancer is one of the most common malignancies worldwide. Histopathologic studies have identified a sequence of changes in the gastric mucosa that mark the slow progression from normal tissue to carcinoma. Epidemiologic evidence suggests that a diet rich in fresh fruit and vegetables could be a protective factor against this disease. This effect may be mediated through antioxidant vitamins.. A randomized, double-blind chemoprevention trial was conducted among 1980 subjects in Tachira State, Venezuela (whose population is at high risk for gastric cancer), to determine the effect of dietary supplementation with vitamin C, vitamin E, and beta-carotene on the progression and regression of precancerous gastric lesions. Subjects were randomly assigned to receive either a combination of vitamin C (750 mg/day), vitamin E (600 mg/day), and beta-carotene (18 mg/day) or placebo for 3 years. Changes in the gastric mucosa were determined by histologic diagnosis based on five biopsies taken from prespecified areas of the stomach at baseline and annually for 3 years. All biopsies were reviewed by a single expert pathologist. Progression rates (and regression rates) were calculated by comparing the first and last available gastroscopies for each subject and dividing the number of subjects whose diagnoses increased (decreased) in severity by the total follow-up time. Overall rate ratios were calculated by Poisson regression, controlling for baseline diagnosis. All statistical tests were two-sided.. Median plasma vitamin levels were increased in the treatment group between baseline and 1 year after randomization from 0.43 micromol/L (interquartile range [IQR] = 0.26-0.69) to 2.89 micromol/L (IQR = 1.76-4.22) for beta-carotene, from 26.7 micromol/L (IQR = 23.1-31.2) to 54.9 micromol/L (IQR = 42.8-67.6) for alpha-tocopherol, and from 47.70 micromol/L (IQR = 36.9-58.5) to 61.9 micromol/L (IQR = 52.2-72.7) for vitamin C. Overall progression rates per 100 person-years were 74.3 in the placebo group and 67.8 in the group randomly assigned to vitamins. Overall regression rates were 109.4 in the placebo group and 116.5 in the group randomly assigned to vitamins. There was no statistically significant difference in progression rate (rate ratio = 0.92, 95% confidence interval [CI] = 0.74 to 1.15) or regression rate (rate ratio = 1.09, 95% CI = 0.90 to 1.33) between vitamin and placebo groups.. Supplementation with antioxidant micronutrients is not an effective tool for gastric cancer control in this high-risk population. The results of this trial are consistent with previous findings on the lack of effect of nutritional supplementation on precancerous gastric lesions.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cell Transformation, Neoplastic; Disease Progression; Double-Blind Method; Female; Gastric Mucosa; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Logistic Models; Male; Middle Aged; Patient Selection; Precancerous Conditions; Risk Assessment; Sample Size; Smoking; Stomach Neoplasms; Treatment Failure; Venezuela; Vitamin E; Vitamins

The importance of dietary modification for disease prevention is widely accepted. The difficulty of implementing and sustaining long-term changes is also well documented. Nevertheless, a few studies have attempted to achieve significant dietary change for extended periods.. The Hiraka Dietary Intervention Study was a community-based randomized cross-over trial designed to develop an effective dietary modification tool and system in an area with high mortality for stomach cancer and stroke in 1998-2000. The main study subjects were 550 healthy volunteers, who were randomized into two groups and given tailored dietary education aimed at decreasing the intake of sodium and increasing that of carotene and vitamin C in either the first or second year. Four (first intervention group) and three (second intervention group) years after the intervention ended, 308 subjects were selected for this follow-up dietary survey.. The low-sodium, high-vitamin C and -carotene diet was maintained with only a small, nonsignificant reversal from post-intervention to follow-up (P = 0.082-0.824). Significant changes from pre-intervention to follow-up were also maintained (P < 0.01).. This dietary intervention program was maintained well over 4 years after the termination of the intervention sessions.

Topics: Ascorbic Acid; Carotenoids; Cross-Over Studies; Feeding Behavior; Follow-Up Studies; Humans; Sodium, Dietary; Stomach Neoplasms; Stroke; Surveys and Questionnaires

Randomized trials have yielded mixed results on the effects of treatment for Helicobacter pylori and little information on the effects of vitamins or garlic supplements on precancerous gastric lesions. We conducted a randomized trial to test the effects of one-time H. pylori treatment and long-term vitamin or garlic supplements in reducing the prevalence of advanced precancerous gastric lesions.. Most of the adults aged 35-64 years in 13 randomly selected villages in Linqu County, Shandong Province, China, were identified and given baseline endoscopies in 1994. In 1995, 3365 eligible subjects were randomly assigned in a factorial design to three interventions or placebos: amoxicillin and omeprazole for 2 weeks in 1995 (H. pylori treatment); vitamin C, vitamin E, and selenium for 7.3 years (vitamin supplement); and aged garlic extract and steam-distilled garlic oil for 7.3 years (garlic supplement). Subjects underwent endoscopies with biopsies in 1999 and 2003, and the prevalence of precancerous gastric lesions was determined by histopathologic examination of seven standard biopsy sites. The 3365 eligible randomized subjects represented 93.5% of those with baseline endoscopy and included all baseline histologic categories except gastric cancer. Only 0.18% had normal gastric mucosa. Logistic regression was used to estimate the intervention effects on the odds of advanced precancerous gastric lesions, and t-tests were used to assess effects on histologic severity. All statistical tests were two-sided.. H. pylori treatment resulted in statistically significant decreases in the combined prevalence of severe chronic atrophic gastritis, intestinal metaplasia, dysplasia, or gastric cancer in 1999 (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.62 to 0.95) and in 2003 (OR = 0.60; 95% CI = 0.47 to 0.75), and had favorable effects on the average histopathologic severity and on progression and regression of precancerous gastric lesions in 2003. H. pylori treatment did not reduce the combined prevalence of dysplasia or gastric cancer. However, fewer subjects receiving H. pylori treatment (19/1130; 1.7%) than receiving placebo (27/1128; 2.4%) developed gastric cancer (adjusted P = .14). No statistically significant favorable effects were seen for garlic or vitamin supplements.. H. pylori treatment reduces the prevalence of precancerous gastric lesions and may reduce gastric cancer incidence, but further data are needed to prove the latter point. Long-term vitamin or garlic supplementation had no beneficial effects on the prevalence of precancerous gastric lesions or on gastric cancer incidence.

Topics: Adult; Amoxicillin; Ascorbic Acid; China; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Factor Analysis, Statistical; Female; Garlic; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Logistic Models; Male; Middle Aged; Omeprazole; Phytotherapy; Precancerous Conditions; Prevalence; Selenium; Severity of Illness Index; Stomach Neoplasms; Vitamin E

A randomized double blind placebo-controlled trial of the drug karinat was carried out in patients with chronic multifocal atrophic gastritis. Karinat contains beta-carotene 2.5 mg, alpha-tocopherol 5 mg, ascorbic acid 30 mg and garlic powder 150 mg per tablet. Out of 66 patients, 34 received karinat, 32--placebo. Both karinat and placebo were administered for 6 months, one tablet twice a day. Karinat therapy improved digestion, the fibrogastroscopic pattern of mucosa, inhibited Helicobacter pylori infection, stimulated stomach activity, mitigated intestinal metaplasia and interfered with the epithelial proliferation of gastric mucosa. These therapeutic effects were more pronounced in the study group. On the whole, the effectiveness of the drug was significantly higher (29%). Karinat should be recommended for the management of chronic atrophic gastritis, a precursor of stomach cancer.

Topics: alpha-Tocopherol; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Chronic Disease; Double-Blind Method; Drug Combinations; Female; Garlic; Gastritis, Atrophic; Helicobacter Infections; Humans; Male; Middle Aged; Plant Extracts; Stomach Neoplasms; Treatment Outcome

This study was aimed at evaluating the effect of long-term vitamin C supplementation on serum and dietary vitamin C and identifying the factors associated with change in serum concentration.. A total of 439 subjects with atrophic gastritis initially participated in a randomized clinical trial using vitamin C and beta-carotene to prevent gastric cancer. We originally randomized the participants into four treatment groups using a 2x2 factorial design, whereby 0 or 15 mg/day beta-carotene and 50 or 500 mg/day vitamin C were administered in a double-blind manner. The beta-carotene component was terminated early after a mean treatment duration of four months. Before and upon early termination of beta-carotene supplementation, 134 subjects dropped out this trial, while 120 and 124 subjects took the vitamin C supplement at either 50 mg or 500 mg daily for five years.. Changes in serum vitamin C were significantly higher in the high-dose group (38.5% increase, 95% CI = 27.0-49.9) than in the low-dose group (13.0% increase, 5.1-20.9) or in the dropout group (3.3% increase, -2.1-8.6) after five-year supplementation. The serum vitamin C at baseline was negatively associated with changes in serum vitamin C (p < 0.0001), while high-dose (p < 0.0001) and low-dose (p < 0.05) supplementation and female gender (p < 0.001) were positively associated. Dietary intake of vitamin C in the supplementation group was almost identical before and after five-year supplementation of vitamin C (2.31 mg/day decrease, 95% CI = -15.3-10.7), while a 17.7 mg/day decrease (95% CI = -44.2-8.86) was observed in the drop-out group.. Five-year vitamin C supplementation induces a remarkable increase in serum vitamin C concentration, and our intervention program appears to have no effect on dietary vitamin C intake.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Diet; Dietary Fiber; Dietary Supplements; Double-Blind Method; Energy Intake; Female; Fruit; Gastritis, Atrophic; Humans; Japan; Male; Middle Aged; Patient Compliance; Stomach Neoplasms; Surveys and Questionnaires; Vegetables

Dietary intervention is one of the important fields in cancer and cardiovascular disease prevention. The Hiraka Dietary Intervention Study is a community-based randomized cross-over trial designed to develop an effective dietary modification tool and system in an area with high mortality of stomach cancer and stroke.. The subjects were 550 healthy volunteers and were randomized into two groups with tailored dietary education to decrease sodium intake and to increase vitamin C and carotene intakes either in the first year (intervention group) or in the second year (control group). Dietary changes were assessed using a validated self-administered diet history questionnaire, fasting blood samples, and 48-hour urine samples, which were obtained before and after the one year period.. During the first year, changes differed significantly between the intervention and control group for both dietary sodium intake (-384 and +255 mg/day, intervention and control respectively, p < 0.001) and urinary sodium excretion (-1003 and -84 mg/day, p < 0.001). Although favorable net changes were also observed in dietary carotene (+418 and +220 mug/day, p < 0.05) and vitamin C (+13 and +2 mg/day, p < 0.05), the serum level differences were modest (+13 and -25 mg/L, p = 0.09 for carotene, +0.1 and -0.5 mg/L, p = 0.07 for ascorbic acid).. The present dietary intervention strategy effectively decreased sodium and increased carotene and vitamin C intakes, although the former was more distinct.

Topics: Aged; Ascorbic Acid; Carotenoids; Community Health Planning; Cross-Over Studies; Diet Surveys; Energy Intake; Feeding Behavior; Female; Follow-Up Studies; Health Education; Humans; Incidence; Japan; Male; Middle Aged; Nutrition Assessment; Nutritional Sciences; Risk Factors; Rural Health; Sodium; Sodium Chloride, Dietary; Sodium, Dietary; Stomach Neoplasms; Surveys and Questionnaires

Free radicals and reactive species produced in vivo can trigger cell damage and DNA modifications resulting in carcinogenesis. Dietary antioxidants trap these species limiting their damage. The present study evaluated the role of vitamins C and E in the prevention of potentially premalignant modifications to DNA in the human stomach by supplementing patients who, because of hypochlorhydria and possible depletion of gastric antioxidants, could be at increased risk of gastric cancer. Patients undergoing surveillance for Barrett's oesophagus (n 100), on long-term proton pump inhibitors were randomized into two groups: vitamin C (500 mg twice/d) and vitamin E (100 mg twice/d) for 12 weeks (the supplemented group) or placebo. Those attending for subsequent endoscopy had gastric juice, plasma and mucosal measurements of vitamin levels and markers of DNA damage. Seventy-two patients completed the study. Plasma ascorbic acid, total vitamin C and vitamin E were elevated in the supplemented group consistent with compliance. Gastric juice ascorbic acid and total vitamin C levels were raised significantly in the supplemented group (P=0.01) but supplementation had no effect on the mucosal level of this vitamin. However, gastric juice ascorbic acid and total vitamin C were within normal ranges in the unsupplemented group. Mucosal malondialdehyde, chemiluminescence and DNA damage levels in the comet assay were unaffected by vitamin supplementation. In conclusion, supplementation does not affect DNA damage in this group of patients. This is probably because long-term inhibition of the gastric proton pump alone does not affect gastric juice ascorbate and therefore does not increase the theoretical risk of gastric cancer because of antioxidant depletion.

Topics: Achlorhydria; Adult; Aged; Antacids; Antioxidants; Ascorbic Acid; Barrett Esophagus; Cell Transformation, Neoplastic; Dietary Supplements; DNA Damage; Female; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Precancerous Conditions; Proton Pump Inhibitors; Stomach Neoplasms; Vitamin E

In a double-blinded randomized controlled trial, we investigated the long-term effect of vitamin C supplementation on blood pressure. A total of 439 Japanese subjects with atrophic gastritis initially participated in the trial using vitamin C and beta-carotene to prevent gastric cancer. Before and on early termination of beta-carotene supplementation, 134 subjects dropped out of this trial, whereas 120 and 124 subjects took the vitamin C supplement daily at either 50 mg or 500 mg, respectively, for 5 years. Before supplementation, neither systolic nor diastolic blood pressure was significantly related with the serum vitamin C concentration. This relationship was unchanged after adjustment for age, body mass index, and alcohol intake or after stratification by gender. After 5 years, systolic blood pressure significantly increased in groups, regardless of vitamin C dose, compared with baseline. Systolic blood pressure in the high-dose group (500 mg daily) increased from 125.4 to 131.7 mm Hg (5.88 mm Hg increase; 95% confidence interval [CI], 3.11 to 8.65). This value was similar with that of the low-dose group (5.73 mm Hg increase; 95% CI, 2.62 to 8.83) and of the dropout group (4.52 mm Hg increase; 95% CI, 1.26 to 7.77). There was no difference in change of diastolic blood pressure among the 3 groups. In conclusion, we observed no reduction in blood pressure with long-term moderate doses (500 mg/day) of vitamin C supplementation in a high-risk population for stomach cancer and stroke.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Blood Pressure; Diastole; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Gastritis, Atrophic; Humans; Hypertension; Japan; Male; Middle Aged; Stomach Neoplasms; Systole; Time; Treatment Outcome

Gastric cancer is the second most frequent cause of death from cancer in the world and the leading cause of death from cancer in China. In September 1995, we launched a randomized multi-intervention trial to inhibit the progression of precancerous gastric lesions in Linqu County, Shandong Province, an area of China with one of the world's highest rates of gastric cancer. Treatment compliance was measured by pill counts and quarterly serum concentrations of vitamin C, vitamin E and S-allyl cysteine. In 1999, toxicity information was collected from each trial participant to evaluate treatment-related side-effects during the trial. Compliance rates were 93% and 92.9% for 39 months of treatment with the vitamins/mineral and garlic preparation, respectively. The means for serum concentrations of vitamins C and E were 7.2 microg/ml and 1695 microg/dl among subjects in the active treatment groups compared with 3.1 microg/ml and 752 microg/dl among subjects in the placebo treatment group, respectively. No significant differences in side-effects were observed between the placebo treatment group and the vitamins/mineral and garlic preparation treatment groups during the 39-month trial period.

Topics: Adult; Aged; Amoxicillin; Antioxidants; Ascorbic Acid; beta Carotene; China; Double-Blind Method; Drug Therapy, Combination; Female; Garlic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Omeprazole; Patient Compliance; Penicillins; Phytotherapy; Plants, Medicinal; Precancerous Conditions; Prevalence; Selenium; Stomach Neoplasms; Treatment Outcome; Vitamin E

Low serum cholesterol has been associated with an increased risk of cancer mortality in various studies, which has led to uncertainty regarding the benefit of lower blood cholesterol.. The aim of our study was to evaluate the association between low blood cholesterol (<5.16 mmol/L) and cancer at sites that have rarely been evaluated. We placed special emphasis on the potential confounding effect of antioxidant vitamins.. Plasma concentrations of cholesterol and antioxidant vitamins were measured in 1971-1973 in 2974 men working in Basel, Switzerland. In 1990, the vital status of all participants was assessed.. Two hundred ninety of the participants had died from cancer, 87 from lung, 30 from prostate, 28 from stomach, and 22 from colon cancer. Group means for plasma cholesterol concentrations did not differ significantly between survivors and those who died from cancer at any of the studied sites. With plasma cholesterol, vitamins C and E, retinol, carotene, smoking, and age accounted for in a Cox model, an increase in total cancer mortality in lung, prostate, and colon but not in stomach cancer mortality was observed in men >60 y of age with low plasma cholesterol. When data from the first 2 y of follow-up were excluded from the analysis, the relative risk estimates remained practically unchanged with regard to lung cancer but decreased for colon, prostate, and overall cancer.. Increased cancer mortality risks associated with low plasma cholesterol were not explained by the confounding effect of antioxidant vitamins, but were attributed in part to the effect of preexisting cancer.

Topics: Age Factors; Ascorbic Acid; Cholesterol; Cohort Studies; Colonic Neoplasms; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Prostatic Neoplasms; Risk Factors; Smoking; Stomach Neoplasms; Switzerland; Vitamin A; Vitamin E

Prior to a randomized controlled trial to prevent gastric cancer by oral supplementation of beta-carotene and vitamin C in a high-risk Japanese population, we examined the serum response to three-month oral supplementation of beta-carotene (0, 3, 30 mg / day) and vitamin C (0, 50, 1000 mg / day) by a three-by-three factorial design using 54 subjects (age range = 40 - 69 years). Serum concentrations of carotenoids, alpha-tocopherol, and ascorbic acid were examined at baseline, and one, two, and three-month points. Both serum beta-carotene and ascorbic acid were significantly higher in high-dose groups than in each placebo group during the supplementation. The serum beta-carotene increased gradually (597 - 830% increase) during the study, whereas the serum ascorbic acid reached nearly a steady-state at the one-month point and remained stable thereafter (88 - 95% increase). No statistically significant interaction between beta-carotene and vitamin C supplementations was observed either for serum beta-carotene or for serum ascorbic acid. Among carotenoids and alpha-tocopherol examined, serum lycopene in the high-dose beta-carotene group was significantly higher than in the placebo group at all points. No unfavorable change in carotenoids and alpha-tocopherol was observed in any group.

Topics: Administration, Oral; Adult; Aged; Analysis of Variance; Ascorbic Acid; beta Carotene; Female; Gastritis, Atrophic; Humans; Japan; Male; Middle Aged; Pilot Projects; Regression Analysis; Stomach Neoplasms; Time Factors; Vitamin E

Previous research has identified a high risk of gastric carcinoma as well as a high prevalence of cancer precursor lesions in rural populations living in the province of Nariño, Colombia, in the Andes Mountains.. A randomized, controlled chemoprevention trial was conducted in subjects with confirmed histologic diagnoses of multifocal nonmetaplastic atrophy and/or intestinal metaplasia, two precancerous lesions. Individuals were assigned to receive anti-Helicobacter pylori triple therapy and/or dietary supplementation with ascorbic acid, beta-carotene, or their corresponding placebos. Gastric biopsy specimens taken at baseline were compared with those taken at 72 months. Relative risks of progression, no change, and regression from multifocal nonmetaplastic atrophy and intestinal metaplasia were analyzed with multivariate polytomous logistic regression models to estimate treatment effects. All statistical tests were two-sided.. All three basic interventions resulted in statistically significant increases in the rates of regression: Relative risks were 4.8 (95% confidence interval [CI] = 1.6-14.2) for anti-H. pylori treatment, 5. 1 (95% CI = 1.7-15.0) for beta-carotene treatment, and 5.0 (95% CI = 1.7-14.4) for ascorbic acid treatment in subjects with atrophy. Corresponding relative risks of regression in subjects with intestinal metaplasia were 3.1 (95% CI = 1.0-9.3), 3.4 (95% CI = 1.1-9.8), and 3.3 (95% CI = 1.1-9.5). Combinations of treatments did not statistically significantly increase the regression rates. Curing the H. pylori infection (which occurred in 74% of the treated subjects) produced a marked and statistically significant increase in the rate of regression of the precursor lesions (relative risks = 8.7 [95% CI = 2.7-28.2] for subjects with atrophy and 5.4 [95% CI = 1.7-17.6] for subjects with intestinal metaplasia).. In the very high-risk population studied, effective anti-H. pylori treatment and dietary supplementation with antioxidant micronutrients may interfere with the precancerous process, mostly by increasing the rate of regression of cancer precursor lesions, and may be an effective strategy to prevent gastric carcinoma.

Topics: Adult; Aged; Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; beta Carotene; Biopsy; Cell Transformation, Neoplastic; Disease Progression; Drug Therapy, Combination; Female; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Logistic Models; Male; Middle Aged; Precancerous Conditions; Remission, Spontaneous; Risk; Stomach; Stomach Neoplasms; Treatment Outcome

In the fall of 1995, 3411 subjects in 13 rural villages in Linqu County, Shandong Province, China, began participating in a blinded, randomized 23 factorial trial to determine whether interventions can reduce the prevalence of dysplasia and other precancerous gastric lesions. One intervention is treatment for infection by Helicobacter pylori with amoxicillin and omeprazole. A second is dietary supplementation with capsules containing vitamin C, vitamin E, and selenium. A third is dietary supplementation with capsules containing steam-distilled garlic oil and Kyolic aged garlic extract. Investigators will evaluate histopathologic endpoints after gastroscopies with biopsies from seven standard sites in 1999. Initial data from pill counts and sampled blood levels of vitamin E, vitamin C, and S-allylcysteine indicate excellent compliance. Subjects have tolerated all interventions well, although 3.1% of those assigned to amoxicillin and omeprazole developed rashes, compared to 0.3% to those in the control group. Preliminary breath tests demonstrate substantial reductions in gastric urease activity, an indication of infection by Helicobacter pylori, among those assigned to amoxicillin and omeprazole.

Topics: Adult; Amoxicillin; Anti-Ulcer Agents; Ascorbic Acid; China; Double-Blind Method; Drug Therapy, Combination; Garlic; Helicobacter Infections; Helicobacter pylori; Humans; Middle Aged; Omeprazole; Penicillins; Phytotherapy; Plant Extracts; Plants, Medicinal; Precancerous Conditions; Selenium; Stomach Neoplasms; Vitamin E

We have initiated a population-based, double-blind, randomized controlled trial to examine the effects of supplementation of beta-carotene and vitamin C on the incidence of gastric cancer. The subjects were participants in an annual health screening program conducted by four municipalities in Akita prefecture, one of the regions with the highest mortality from gastric cancer in Japan. We measured their serum levels of pepsinogens (PGs) I and II, and asked persons diagnosed with chronic atrophic gastritis (defined as PG I < 70 ng/ml and PG I/PG II ratio < 3.0) to take diet supplements containing 0 or 15 mg/day beta-carotene and 50 or 500 mg/day vitamin C for 5 years. During the first year of recruitment conducted in one village from June through September, 1995, 52% (635/1214) of screening participants had chronic atrophic gastritis and 73% (439/602) of eligible persons responded. However, in response to a National Cancer Institute press report released on January 18, 1996, indicating that two beta-carotene trials had shown no benefit and potential harm from the supplement, we discontinued the beta-carotene and continued with the trial using only vitamin C. Of 397 participants remaining at this point, 77% (305) consented to stay in the study. The results indicate that a randomized controlled trial for cancer prevention is feasible in the Japanese asymptomatic population.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Double-Blind Method; Female; Humans; Japan; Male; Middle Aged; Risk Factors; Stomach Neoplasms

Low intake of foods rich in vitamin C is associated with an increased risk of gastric cancer, and geographic variation in average vitamin C intake, therefore, could explain some of the wide international variation in gastric cancer rates. This multicentre study investigated the relationships between plasma levels of vitamin C, as an indicator of vitamin C intake, and gastric cancer rates, markers of gastritis and other socio-demographic variables. Fasting plasma samples from about 1,400 individuals from 9 centres in 7 countries worldwide were assayed for total vitamin C using a fluorometric assay. There was no association between average plasma vitamin C levels and either gastric cancer mortality or incidence rates in the populations studied. Therefore, variation in fasting plasma vitamin C levels, as an indicator of consumption of vitamin C, does not appear to explain any of the wide geographic variation in gastric cancer rates. Furthermore, there was no association between plasma vitamin C levels and Helicobacter pylori infection, low serum levels of pepsinogen A (as a marker of severe chronic atrophic gastritis) or the presence of DNA adducts in blood leukocyte DNA. Multivariate models showed that fasting plasma vitamin C levels were associated positively with female sex, higher levels of education, never having smoked and increasing height and negatively with number of cigarettes smoked per day and increasing weight. This suggests not only that gender and tobacco smoking, in particular, are important predictors of plasma vitamin C levels but also that their effects are consistent throughout the developed world.

Topics: Adult; Antigens, Bacterial; Ascorbic Acid; Cross-Sectional Studies; DNA Adducts; Educational Status; Female; Gastritis; Humans; International Cooperation; Male; Middle Aged; Multivariate Analysis; Pepsinogens; Sex Factors; Smoking; Socioeconomic Factors; Stomach Neoplasms

A randomized chemoprevention trial on precancerous lesions of the stomach is being conducted in Tachira State, Venezuela. The aims of the study are to evaluate the efficacy of vitamin supplementation in preventing the progression rate of precancerous lesions. Here we report on the pilot phase of the study in which two antioxidant preparations were evaluated on their ability to raise antioxidant levels in plasma and in gastric juice. The study aimed also to determine the antibiotic sensitivity profiles of Helicobacter pylori isolates prevalent in the area. Forty-three subjects with precancerous lesions (chronic gastritis, chronic atrophic gastritis, intestinal metaplasia and dysplasia) of the stomach were randomized to one of two antioxidant treatments. Treatment 1 (250 mg of standard vitamin C, 200 mg of vitamin E and 6 mg of beta-carotene three times a day) or treatment 2 (150 mg of standard vitamin C, 500 mg of slow release vitamin C, 75 mg of vitamin E and 15 mg of beta-carotene once a day) for 7 days. Blood levels of total vitamin C, beta-carotene and alpha-tocopherol and gastric juice levels of ascorbic acid and total vitamin C were measured before and after treatment on day 8. Both treatments increased the plasma levels of total vitamin C, beta-carotene and alpha-tocopherol/cholesterol but not those of ascorbic acid or total vitamin C in gastric juice. Treatment 1 was the best choice and resulted in a greater increase in the plasma levels of beta-carotene and alpha-tocopherol. H. pylori was cultured from 90% of the gastric biopsies; 35 isolates were identified which were highly resistant to metronidazole, a front-line antibiotic recommended against H. pylori in other settings.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Chemoprevention; Chronic Disease; Disease Progression; Female; Gastric Juice; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metaplasia; Middle Aged; Pilot Projects; Precancerous Conditions; Stomach Neoplasms; Venezuela; Vitamin E; Vitamins

Observational epidemiological studies suggest that some nutrients reduce the risk of gastric cancer and that individuals with atrophic gastritis are at high risk of developing gastric cancer. One possible measure for gastric cancer prevention is therefore nutritional supplementation for the high risk group. Before recommending this strategy for the general public, however, a randomized controlled trial (RCT) is necessary. To evaluate the feasibility of an RCT, the authors conducted a pilot study using recipients of a health check-up program in a general hospital in Japan. The subjects who were asked to participate in the trial had been diagnosed as having atrophic gastritis on the basis of serum pepsinogen I < 70 ng/ml and the ratio of pepsinogen I to II < 3.0. They were requested to ingest double-blinded capsules containing different levels of vitamin C and beta-carotene every day. Out of the 219 subjects (118 males, 101 females) who were eligible for the study and had the required pepsinogen measurement, 90 (41%) met the criteria for atrophic gastritis. Among them, 55 (61%) (35 males, 20 females) gave their informed consent to participate in the RCT. Fifty-four participants completed a 3-month course of supplementation, and all of them agreed to a 5-year supplementation period. The authors concluded that an RCT using double-blinded nutritional supplements and targeting apparently healthy individuals is feasible in an intervention study for cancer prevention in Japan.

Topics: Adult; Aged; Anticarcinogenic Agents; Ascorbic Acid; beta Carotene; Carotenoids; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Compliance; Pilot Projects; Randomized Controlled Trials as Topic; Research Design; Stomach Neoplasms

Topics: Ascorbic Acid; Clarithromycin; Double-Blind Method; Drug Combinations; Europe; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Omeprazole; Placebos; Stomach Neoplasms

A randomized nutrition intervention trial was conducted among 29,584 adult residents of Linxian, China, to examine the effects of vitamin/mineral supplementation on the occurrence of esophageal/gastric cardia cancer in this high-risk population. A fractional factorial study design allowed evaluations of four different combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta-carotene, vitamin E, and selenium. During the 5.25-year intervention, significant reductions in total mortality, total cancer mortality, and stomach cancer mortality occurred among those receiving beta-carotene, vitamin E, and selenium. At the end of intervention, an endoscopic survey was carried out in a sample of subjects to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus or stomach. Endoscopy was performed on 391 individuals from two study villages. The prevalences of esophageal and gastric dysplasia and cancer were compared by nutrient factor. Cancer or dysplasia was diagnosed in 15% of the participants. No statistically significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen for any of the four vitamin/mineral combinations. The greatest reduction in risk (odds ratio, 0.38; P = 0.09) was seen for the effect of retinol and zinc on the prevalence of gastric cancer. Although no significant protective effects were seen in this endoscopic survey, there was a suggestion that supplementation with retinol and zinc may protect against the development of gastric neoplasia in this high-risk population. Additional studies with larger numbers of endpoints will be needed to further evaluate this possibility.

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; China; Cross-Cultural Comparison; Cross-Sectional Studies; Double-Blind Method; Endoscopy, Gastrointestinal; Esophageal Neoplasms; Esophagus; Female; Gastric Mucosa; Humans; Incidence; Male; Middle Aged; Minerals; Molybdenum; Niacin; Precancerous Conditions; Riboflavin; Rural Population; Selenium; Stomach Neoplasms; Survival Rate; Vitamin A; Vitamin E; Vitamins; Zinc

Linxian, China has some of the highest rates of esophageal/gastric cardia cancer in the world, and epidemiological evidence suggests that chronically low intake of micronutrients may contribute to these high cancer rates. To examine whether supplementation with multiple vitamins and minerals can affect the occurrence of esophageal/gastric cardia cancer in this population, a two-arm randomized nutrition intervention trial was conducted among 3318 Linxian residents with cytological evidence of esophageal dysplasia. During the 6-year intervention, esophageal/gastric cardia cancer mortality was 8% lower among those receiving the active supplements. After 30 and 72 months of intervention, endoscopic surveys were carried out to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus and stomach. In the first survey, in 1987, 833 subjects were endoscoped; in the second survey, in 1991, 396 subjects were examined. The histological diagnoses from each survey were compared by treatment group. Cancer or dysplasia was diagnosed in 28% of the subjects endoscoped in 1987 and 24% of those examined in 1991. The odds ratio for subjects in the treatment group (versus those in the placebo group) having esophageal or gastric dysplasia or cancer was 0.84 (95% confidence interval, 0.61-1.15) in 1987 and 0.86 (0.54-1.38) in 1991. Although modest protective effects on worst overall diagnosis were seen in the supplemented group in both surveys, none of the results was statistically significant, and the findings must be considered inconclusive.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; Cross-Cultural Comparison; Double-Blind Method; Endoscopy, Gastrointestinal; Esophageal Neoplasms; Esophagus; Female; Follow-Up Studies; Gastric Mucosa; Humans; Male; Middle Aged; Minerals; Molybdenum; Niacin; Precancerous Conditions; Riboflavin; Rural Population; Selenium; Stomach Neoplasms; Survival Rate; Vitamin A; Vitamin E; Vitamins; Zinc

In Linxian China, the esophageal/gastric cardia cancer mortality rates are among the highest in the world. There is suspicion that the population's chronic deficiencies of multiple micronutrients are etiologically involved. We conducted two randomized, placebo-controlled nutrition intervention trials to test the effects of vitamin and mineral supplements in lowering the rates of esophageal/gastric cancer. In the first trial, the dysplasia trial, 3318 adults with a cytological diagnosis of esophageal dysplasia received daily supplementation with 26 vitamins and minerals in doses typically 2-3 times the United States Recommended Daily Allowances, or placebos, for 6 years. The second trial, the general population trial, involved 29,584 adults and used a one-half replicate of a 2(4) factorial experimental design which tested the effects of four combinations of nutrients: A, retinol and zinc; B, riboflavin and niacin; C, vitamin C and molybdenum; and D, beta-carotene, vitamin E, and selenium. Doses for these daily supplements ranged from 1 to 2 times the United States Recommended Daily Allowances, and the different vitamin/mineral combinations or placebos were taken for a period of 5.25 years. As part of the general population trial, and end-of-intervention endoscopy survey was carried out in a small (1.3%) sample of subjects to see if supplementation affected the prevalence of dysplasia and early cancer. Herein we review the methods of these trials and the results of the endoscopic survey. Fifteen esophageal and 16 gastric cancers were identified in endoscopic biopsies from the 391 subjects evaluated from two villages, and nearly all were asymptomatic. No significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen with any of the four supplement groups. However, the prevalence of gastric cancer among participants receiving retinol and zinc was 62% lower than those not receiving those supplements (P = 0.09), while participants receiving beta-carotene, vitamin E, and selenium had a 42% reduction in esophageal cancer prevalence (0.34). We have reported separately that cancer mortality over the entire 5.25-year period was significantly reduced among those receiving beta-carotene, vitamin E, and selenium. The findings from the overall trial and the endoscopic sample offer a hopeful sign and should encourage additional studies with these agents in larger numbers of subjects.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Biopsy; Carotenoids; China; Diet; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Niacin; Nutritional Physiological Phenomena; Odds Ratio; Precancerous Conditions; Riboflavin; Selenium; Stomach Neoplasms; Vitamin A; Vitamin E; Zinc

The suitability of complex administration of antioxidants (vitamins C, E and A) for prevention of postoperative complications was assessed in a randomized study which included 197 cases of gastric cancer. The treatment was followed by a lowering of lipid peroxidation process. In a group of 95 patients who had received the drugs preoperatively, the postoperative complication rate dropped from 30.9 to 1.9%.

Topics: Antioxidants; Ascorbic Acid; Energy Metabolism; Humans; Lipid Peroxidation; Peptides; Postoperative Complications; Stomach Neoplasms; Vitamin A; Vitamin E

Smoking is a risk factor for gastric cancer (GC) and causes oxidative stress. Antioxidant vitamins may protect against oxidative stress. This study aimed to determine the association between dietary antioxidant vitamin intake and GC risk according to smoking status and the histological subtype. This case-control study included 286 pairs of patients with GC and controls aged 20-79 years enrolled at two hospitals from 2002 to 2006, matched by age (± 2 years), sex, hospital, and participation period (± 1 years). Dietary information was collected using a quantitative food frequency questionnaire (FFQ). When stratified by smoking status, increased intake of vitamin C (OR = 0.38; 95% CI = 0.17-0.84 for highest vs. lowest;

Topics: Antioxidants; Ascorbic Acid; Case-Control Studies; Diet; Folic Acid; Humans; Republic of Korea; Risk Factors; Smoking; Stomach Neoplasms; Vitamins

Topics: Antioxidants; Ascorbic Acid; Beta vulgaris; Carotenoids; Daucus carota; Flavonoids; Fruit; Humans; Phenols; Phyllanthus emblica; Phytochemicals; Plant Extracts; Solanum lycopersicum; Stomach Neoplasms

To investigate the effects of piperlongumine (PL) and vitamin C (VC) on signal transducer and activator of transcription 3 (STAT3) signalling in gastric cancer cell lines.. Both PL and VC induced apoptosis and inhibited cell proliferation in AGS and KATO III cells. These effects were dependent on reactive oxygen species (ROS). PL effectively suppressed STAT3 activation while VC caused abnormal activation of STAT3. The combination of PL and VC exhibited a stronger apoptotic effect compared with either agent alone. PL reversed the abnormal activation of STAT3 by VC, which could be a key to their synergistic effect.. PL combined with VC exhibited a stronger anticancer effect by regulating the ROS-STAT3 pathway, suggesting that this combination might be a potential adjuvant therapy for gastric cancer.

Topics: Ascorbic Acid; Cell Line, Tumor; Chemotherapy, Adjuvant; Dioxolanes; Humans; Reactive Oxygen Species; STAT3 Transcription Factor; Stomach Neoplasms

Cancers of digestive tract such as colorectal cancer (CRC) and gastric cancer (GC) are the most commonly detected types of cancer worldwide and their origin can be associated with oxidative stress conditions. Commonly known and followed antioxidants, such as vitamin C and E, are widely considered as potential anti-cancer agents. Raman spectra have great potential in the biochemical characterization of matter based on the fact that each molecule has its own unique vibrational properties. Raman spectroscopy allows to precisely characterize components (proteins, lipids, nucleic acids). The paper presents the application of the Raman spectroscopy technique for the analysis of tissue samples and cells of the human colon and stomach. The main goal of this study is to show the differences between healthy and cancerous tissues from the human digestive tract and human normal and cancer colon and gastric cell lines. The paper presents the spectroscopic characterization of normal colon cells, CCD-18 Co, in physiological and oxidative conditions and effect of oxidative injury of normal colon cells upon supplementation with vitamin C at various concentrations based on Raman spectra. The obtained results were related to the Raman spectra recorded for human colon cancer cells-CaCo-2. In addition, the effect of the antioxidant in the form of vitamin E on gastric cancer cells, HTB-135, is presented and compared with normal gastric cells-CRL-7869. All measured gastric samples were biochemically and structurally characterized by means of Raman spectroscopy and imaging. Statistically assisted analysis has shown that normal, ROS injured and cancerous human gastrointestinal cells can be distinguished based on their unique vibrational properties. ANOVA tests, PCA (Principal Component Analysis) and PLSDA (Partial Least Squares Discriminant Analysis) have confirmed the main role of nucleic acids, proteins and lipids in differentiation of human colon and stomach normal and cancer tissues and cells. The conducted research based on Raman spectra proved that antioxidants in the form of vitamin C and E exhibit anti-cancer properties. In consequence, conducted studies proved that label-free Raman spectroscopy may play an important role in clinical diagnostic differentiation of human normal and cancerous gastrointestinal tissues and may be a source of intraoperative information supporting histopathological analysis.

Topics: Ascorbic Acid; Caco-2 Cells; Colonic Neoplasms; Dietary Supplements; Humans; Lipids; Nucleic Acids; Principal Component Analysis; Spectrum Analysis, Raman; Stomach Neoplasms

Tissue factor (TF), the trigger protein of the extrinsic blood coagulation cascade, is abundantly expressed in various cancers including gastric cancer. Anti-TF monoclonal antibodies (mAbs) capable of targeting cancers have been successfully applied to armed antibodies such as antibody-drug conjugates (ADCs) and molecular imaging probes. We prepared an anti-TF mAb, clone 1084, labeled with astatine-211 (

Topics: Animals; Antibodies, Monoclonal, Humanized; Ascorbic Acid; Astatine; Blood Coagulation; Body Weight; Cell Line, Tumor; Female; Heterografts; Humans; Immunoconjugates; Linear Energy Transfer; Mice; Mice, Inbred BALB C; Mice, Nude; Protein Denaturation; Radiation-Protective Agents; Radioimmunotherapy; Receptor, ErbB-2; Stomach Neoplasms; Thromboplastin

Vitamin C has re-emerged as a promising anticancer agent. This study attempts to analyze the differential gene expression of profiles GSE11919 to look for some clues, and the most significant cell cycle pathway caused by vitamin C was identified by integrated bioinformatics analysis. Inspired by this, we investigated the effect of vitamin C treatment on gastric carcinoma cells by detection of cell cycle, apoptosis, and autophagy. Vitamin C significantly elevated the percentage of cells at G0/G1 phase, whereas the percentage of S phase cells was decreased. Meanwhile, vitamin C treatment resulted in downregulation of cell cycle-related protein Cyclin D1. We deduced that the downregulation of Cyclin D1 by vitamin C accompanied by significantly increased 5'AMP-activated protein kinase and induced autophagy in MKN45 cells. These results suggest that vitamin C has the antiproliferation effect on gastric carcinoma cells via the regulation of cell cycle and autophagy by Cyclin D1.

Topics: Ascorbic Acid; Autophagy; Cell Line, Tumor; Cell Proliferation; Cyclin D1; Down-Regulation; G1 Phase; Gene Expression Profiling; Humans; Stomach Neoplasms

Ascorbic acid, known as vitamin C, has been used in combination with a number of cytotoxic agents in vitro and in vivo with contradictory results on its effectiveness. It is believed that vitamin C can sensitize different cancer cells to common therapy strategies such as chemotherapy and radiotherapy. During current research, the combination effect of vitamin C with cisplatin was evaluated against gastric cancer cells.. MTT-based proliferation assay, combination index method, and flow cytometry technique were employed for the assessment of cell cycle and determination of apoptosis/necrosis on the AGS cell line.. Co-treatment of gastric cancer cells with vitamin C in its IC50 dose in addition to cisplatin in both IC50 (10 µg/ml) and five times less (2 µg/ml) doses could increase the cytotoxicity effect of cisplatin in a synergistic manner. Moreover, the pointed co-treatment approach could induce the cell count in sub-G0 phase while reducing it in the G0/G1, G2/M, and S phases. Further findings showed that the combined dose of vitamin C and cisplatin could increase the percentage of apoptotic and necrotic cells in comparison with a single dose of cisplatin.. This study introduces a possible approach for the treatment of gastric cancer with more potency and less amount of administered cisplatin to induce toxicity.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Ascorbic Acid; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Cisplatin; Drug Synergism; Humans; Stomach; Stomach Neoplasms

Topics: Animals; Antineoplastic Agents; Apoptosis; Ascorbic Acid; Cell Line, Tumor; Cell Proliferation; Drug Synergism; Female; Glucose Transporter Type 1; Glutathione; Humans; Irinotecan; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Models, Biological; Oxaliplatin; Oxidation-Reduction; Oxidative Stress; Prognosis; Reactive Oxygen Species; Stomach Neoplasms; Treatment Outcome; Xenograft Model Antitumor Assays

Gastric adenocarcinoma most often presents at an advanced stage and overall five-year survival of ∼30%. Pharmacological ascorbate (high-dose IV ascorbate) has been proposed as a promising nontoxic adjuvant to standard radio-chemotherapies in several cancer types. In the current study, pharmacological ascorbate (0.5-2 m M) caused a dose-dependent decrease (70-85% at 2 m M) in clonogenic survival of gastric adenocarcinoma cells (AGS and MNK-45), but was relatively nontoxic to a small intestinal epithelial nonimmortalized human cell isolate (FHs 74 Int). The addition of pharmacological ascorbate (1 m M) to standard radio-chemotherapies [i.e., 5-FU (5 μ M); cisplatin (0.5 μ M); irinotecan (2.5 μ M); carboplatin (5 μ M); paclitaxel (2-4 n M); and X rays (1.8 Gy)] also potentiated gastric cancer clonogenic cell killing [additional decreases were noted with: ascorbate plus 5-FU/radiation (1%); ascorbate plus cisplatin/irinotecan (9-19%); and ascorbate plus paclitaxel/carboplatin (6-7%)]. The gastric cancer cell toxicity and chemosensitization seen with pharmacological ascorbate was dependent on H

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Cell Line, Tumor; Chemoradiotherapy; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Synergism; Female; Humans; Mice; Stomach Neoplasms; Xenograft Model Antitumor Assays

The recently reported results of Lu

Topics: Ascorbic Acid; Cell Line, Tumor; Humans; Oxaliplatin; Oxidation-Reduction; Stomach Neoplasms

To investigate the effects of dietary vitamin C and foods containing vitamin C on gastric cancer risk.. Our study included 830 control subjects and 415 patients. Data regarding demographics, medical history, and lifestyle, including dietary and nutrient intake, were collected using reliable self-administered questionnaires. Dietary intake information was collected from the participants using a food frequency questionnaire that has been previously reported as reliable and valid. A rapid urease test and a histological evaluation were used to determine the presence of Helicobacter pylori (H. pylori) infection. Twenty-three vitamin C-contributing foods were selected, representing over 80% of the cumulative vitamin C contribution.. In analyses adjusted for first-degree family history of gastric cancer, education level, job, household income, smoking status, and regular exercise, an inverse association between vitamin C intake and gastric cancer risk was observed for the highest (≥ 120.67 mg/d) vs the lowest (< 80.14 mg/d) intake category [OR (95%CI): 0.64 (0.46-0.88)], with a significant trend across the three intake categories (P = 0.007). No protective effect of vitamin C was detected after stratification by gender. No effect of vitamin C intake on the gastric cancer incidence was found in either men or women infected with H. pylori. Vitamin C-contributing foods, including cabbage [0.45 (0.32-0.63), 0.50 (0.34-0.75), 0.45 (0.25-0.81)], strawberries [0.56 (0.40-0.78), 0.49 (0.32-0.74), 0.52 (0.29-0.93)], and bananas [0.40 (0.29-0.57), 0.41 (0.27-0.62), 0.34 (0.19-0.63)], were protective factors against the risk of gastric cancer based on the results of the overall adjusted analyses and the results for men and women, respectively.. A protective effect of vitamin C and vitamin C-contributing foods against gastric cancer was observed. Further studies using larger sample sizes are required to replicate our results.

Topics: Adult; Ascorbic Acid; Carcinoma; Case-Control Studies; Diet; Dietary Carbohydrates; Energy Intake; Female; Fruit; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Male; Middle Aged; Protective Factors; Republic of Korea; Risk Factors; Solanum tuberosum; Stomach Neoplasms; Surveys and Questionnaires

Since its discovery in 1982, the global importance of Helicobacter pylori-induced disease, particularly in developing countries, remains high. The use of rodent models, particularly mice, and the unanticipated usefulness of the gerbil to study H. pylori pathogenesis have been used extensively to study the interactions of the host, the pathogen, and the environmental conditions influencing the outcome of persistent H. pylori infection. Dietary factors in humans are increasingly recognized as being important factors in modulating progression and severity of H. pylori-induced gastric cancer. Studies using rodent models to verify and help explain mechanisms whereby various dietary ingredients impact disease outcome should continue to be extremely productive.

Topics: Animals; Ascorbic Acid; Developing Countries; Diet; Dietary Fats; Disease Models, Animal; Folic Acid; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Humans; Mice; Salts; Stomach Neoplasms

The aim of the paper was to determine the level of antioxidants and metabolomic fingerprinting in both raw beetroots and naturally fermented beetroot juices from organic (ORG) versus conventional (CONV) production. In addition, the anticancer properties of the fermented beetroot juices were evaluated.. The obtained results showed that ORG fresh beetroots contained significantly more dry matter, vitamin C and some individual phenolic compounds than CONV beetroots. The content of total phenolic acids was significantly higher in CONV beetroots compared with the ORG ones. The level of flavonoids was similar in ORG and CONV beetroots. There were only slight differences in the chemical composition of ORG and CONV beetroot juices. Metabolomic analysis provided a possibility to distinguish clearly between ORG and CONV fermented beetroot juices. However, this method was less useful in the case of fresh whole beetroots. It was found that anticancer activity was stronger in the case of ORG fermented juices when compared with CONV ones.. The obtained results indicate that ORG- and CONV-produced beetroots and fermented beetroot juices have different chemical properties and different impacts on cancer cells. It is necessary to continue research on this topic in order to confirm and understand the achieved results.

Topics: Adenocarcinoma; Anticarcinogenic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Beta vulgaris; Beverages; Cell Line, Tumor; Chromatography, High Pressure Liquid; Fermentation; Flavonoids; Food Inspection; Food, Organic; Humans; Metabolome; Phenols; Plant Roots; Poland; Spectrometry, Mass, Electrospray Ionization; Stomach Neoplasms

Dietary N-nitroso compounds and endogenous nitrosation are important carcinogenic factors, but human evidence of their role is scarce for esophageal cancer and inconsistent for gastric cancer.. We studied the relation between risks of esophageal and gastric cancer subtypes and dietary intake of N-nitrosodimethylamine, heme iron, nitrite, and nitrate in the Netherlands Cohort Study.. A total of 120,852 men and women aged 55-69 y were recruited in 1986, and diet, based on a 150-item food-frequency questionnaire, and other risk factors were assessed. The cohort was followed for 16.3 y, and 110 esophageal squamous cell carcinoma (ESCC), 151 esophageal adenocarcinoma, 166 gastric cardia adenocarcinoma, and 497 gastric noncardia adenocarcinoma (GNCA) cases were analyzed along with 4032 subcohort members in a case-cohort analysis.. Positive associations were observed between N-nitrosodimethylamine intake and ESCC risk (HR for 0.1-μg/d increase in intake: 1.15; 95% CI: 1.05, 1.25; P-trend = 0.01 based on tertiles of intake) and GNCA risk (1.06; 95% CI: 1.01, 1.10; P-trend = 0.09) in men. ESCC risk was associated with nitrite intake (HR for 0.1-mg/d increase: 1.19; 95% CI: 1.05, 1.36; P-trend = 0.06) and heme-iron intake (HR for 1-mg/d increase: 1.83; 95% CI: 0.98, 3.39; P-trend = 0.03). Among women, exposure levels were lower, and we found no convincing positive associations.. These results suggest that N-nitroso compounds may influence the risk of ESCC in men, but there are no clear associations for other esophageal and gastric subtypes.

Topics: Aged; Ascorbic Acid; Chlorophyll; Diet; Dimethylnitrosamine; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Iron, Dietary; Linear Models; Male; Middle Aged; Multivariate Analysis; Netherlands; Nitrates; Nitrites; Nitrosation; Prospective Studies; Risk Assessment; Risk Factors; Stomach Neoplasms; Surveys and Questionnaires

Berries and berry extracts possess properties that make them important in the prevention of cancer. The high antioxidant levels of these extracts play a role, but components of the berries can have other effects on cell replication and survival. We chose to test the hypothesis that (i) although the antioxidant capacity of raspberry extracts is important for inhibiting the proliferation of tumor cells, other characteristics of the berry extracts are responsible for a major part of their antiproliferative activity, and that (ii) the relative importance of the antioxidant effect can depend on the cell type being studied. The aim of this study was to assess the relative roles of low pH and high antioxidant levels in the killing of 3 cell types by an aqueous extract from Meeker red raspberries. Stomach, colon, and breast cancer cells were treated with berry extract and with HCl and ascorbic acid solutions of the same pH. A dilution of 7.5% ascorbic acid solution, of the same pH and slightly higher antioxidant concentration than the berry extract, killed less than 10% of the stomach and colon cancer cells. In contrast, the berry extract at this same dilution killed more than 90% of these cells. Antioxidants played a more significant role in the killing of breast cancer cells, however. For these cells, approximately 50% of the killing could be attributed to antioxidant effects. We conclude that the antioxidant effect plays a minor role in the killing of 2 gastrointestinal cell types, but its role in inactivating a breast cancer cell line is much more significant. No evidence of apoptosis was observed, and caspase activation did not contribute to cell killing by the extract.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Breast Neoplasms; Caspases; Cell Division; Cell Line, Tumor; Colonic Neoplasms; Fruit; Humans; Phytotherapy; Plant Extracts; Stomach Neoplasms

We investigated the molecular mechanism by which ascorbic acid (AA) induces apoptosis in human gastric cancer cells, AGS cells. High concentration (more than 5mM) of AA increased cellular iron uptake by increasing transferrin receptor (TfR) expression and induced AGS cell apoptosis which was inhibited by catalase. Interestingly, p38 mitogen-activated protein kinase (MAPK) inhibitor inhibited the upregulation of TfR and increased cell survival by AA. TfR-siRNA-transfected cells reduced apoptosis by AA. H(2)O(2) increased TfR expression in AGS cells. Taken together, we concluded that high concentration of AA, through H(2)O(2), induces apoptosis of AGS cells by p38-MAPK-dependent upregulation of TfR.

Topics: Apoptosis; Ascorbic Acid; Catalase; Cell Line, Tumor; Cell Survival; DNA Breaks; Humans; Hydrogen Peroxide; Imidazoles; Iron; p38 Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins c-bcl-2; Pyridines; Receptors, Transferrin; Stomach Neoplasms; Up-Regulation

Higher ascorbic acid consumption is associated with a reduced risk of gastric cancer in numerous epidemiologic studies. We investigated whether single nucleotide polymorphisms (SNPs) in SLC23A1 and SLC23A2--genes that encode key ascorbic acid transport proteins--affect gastric cancer risk in 279 incident cases and 414 age- and gender-matched controls drawn from a population-based case-control study in Poland. Compared to subjects who were homozygous for the common G allele of the SLC23A2 SNP rs12479919, carriers of the AA genotype had a 41% lower risk of gastric cancer [odds ratio (OR)=0.59, 95% confidence interval (CI): 0.36-0.95; P trend=0.06]. A haplotype that contained the common allele of the rs6139591, rs2681116 and rs14147458 SNPs in SLC23A2 was also significantly inversely associated with gastric malignancy. No other polymorphisms in either gene were related to risk, and there was no effect modification by ascorbic acid intake. These findings suggest that genetic variation in SLC23A2 impacts gastric cancer risk, although confirmation in other studies is required.

Topics: Adult; Age Distribution; Aged; Ascorbic Acid; Case-Control Studies; Diet; Female; Genetic Predisposition to Disease; Genetic Variation; Genotype; Humans; Male; Middle Aged; Organic Anion Transporters, Sodium-Dependent; Polymorphism, Single Nucleotide; Sex Distribution; Sodium-Coupled Vitamin C Transporters; Stomach Neoplasms; Symporters; Young Adult

In traditional Korean medicine, lotus (Nelumbo nucifera Gaertn) roots have been used as an antidiabetic and an antiproliferative remedy. However, scientific publications on lotus properties are very limited. Therefore, it was decided to investigate the Korean white lotus cultivars in order to find out their bioactivity. It was found that all lotus cultivars (Inchisa, Muan, Garam, and Chungyang) possess high amounts of bioactive compounds: total phenols, between 7.95 +/- 0.8 and 4.21 +/- 0.3 mg of gallic acid equivalents (GAE)/g dry weight (DW); ascorbic acid, between 15.8 +/- 1.1 and 22.3 +/- 1.7 mg of ascorbic acid/g DW; and amino acids, between 15.05 +/- 0.82% and 16.62 +/- 0.90% DW. The highest contents of polyphenols (7.95 +/- 0.8 mg of GAE/g DW) and the highest levels of antioxidant [by 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) and 1,1-diphenyl-2-picrylhydrazyl assays, 54.27 +/- 6.1 and 21.98 +/- 2.5 microM Trolox equivalents/g DW, respectively] and antiproliferative activities on both human cancer cell lines (Calu-6 for human pulmonary carcinoma and SMU-601 for human gastric carcinoma, 59.75 +/- 3.99% and 71.21 +/- 2.79% cell viability, respectively) were found in the Chungyang cultivar. Fluorometry and Fourier transform infrared spectroscopy can be applied as rapid methods for determination of bioactive compounds, such as polyphenols. The correlation between the bioactive compounds and the antioxidant activity was high. In conclusion, all Korean white lotus cultivars are valuable medicinal foods, and in order to receive the best results a combination of lotus cultivars has to be consumed.

Topics: Amino Acids; Antineoplastic Agents, Phytogenic; Antioxidants; Ascorbic Acid; Cell Line, Tumor; Cell Proliferation; Cell Survival; Fluorometry; Gallic Acid; Humans; Lung Neoplasms; Nelumbo; Neoplasms; Phenols; Plant Extracts; Plant Roots; Spectroscopy, Fourier Transform Infrared; Stomach Neoplasms

In human studies, low vitamin C intake has been associated with more severe Helicobacter pylori gastritis and a higher incidence of gastric cancer. However, vitamin C supplementation has not been definitively shown to protect against gastric cancer. Using vitamin C-deficient B6.129P2-Gulo(tm1Umc/mmcd) (gulo(-/-)) mice lacking L-gulono-gamma-lactone oxidase, we compared gastric lesions and Th1 immune responses in H. pylori-infected gulo(-/-) mice supplemented with low (33 mg/L) or high (3,300 mg/L) vitamin C in drinking water for 16 or 32 weeks. Vitamin C levels in plasma and gastric tissue correlated with the vitamin C supplementation levels in gulo(-/-) mice. H. pylori infection resulted in comparable gastritis and premalignant lesions in wildtype C57BL/6 and gulo(-/-) mice supplemented with high vitamin C, but lesions were less severe in gulo(-/-) mice supplemented with low vitamin C at 32 weeks post infection. The reduced gastric lesions in infected gulo(-/-) mice supplemented with low vitamin C correlated with reduced Th1-associated IgG2c, gastric IFN-gamma and TNF-alpha mRNA and higher H. pylori colonization levels. These results in the H. pylori-infected gulo(-/-) mouse model suggest that although supplementation with a high level of vitamin C achieved physiologically normal vitamin C levels in plasma and gastric tissue, this dose of vitamin C did not protect gulo(-/-) mice from H. pylori-induced premalignant gastric lesions. In addition, less severe gastric lesions in H.pylori infected gulo(-/-) mice supplemented with low vitamin C correlated with an attenuated Th1 inflammatory response.

Topics: Animals; Ascorbic Acid; Chromatography, High Pressure Liquid; Dietary Supplements; Female; Gastritis; Helicobacter Infections; Interferon-gamma; L-Gulonolactone Oxidase; Male; Mice; Mice, Inbred C57BL; Polymerase Chain Reaction; Precancerous Conditions; Receptors, IgG; Sex Factors; Stomach Neoplasms; Th1 Cells; Tumor Necrosis Factor-alpha

Mycoplasma hyorhinis (M. hyorhinis) exerts multiple effects on cell metabolisms including apoptosis mediated by their endonucleases and nitric oxide production in vitro. Although AsA is preferable to health in general because of its reactive oxygen species scavenging activity, we found that in a human carcinoma cell line AZ-521 infected with M. hyorhinis, apoptosis was enhanced by addition of L-ascorbic acid (AsA) to the cell cultures. No significant differences were evident between the AZ-521 cells with and without AsA (AsA-) after 24 hr of incubation in the mitochondrial fluorescence. M. hyorhinis-infected AZ-521 cells treated with AsA (AsA +) have developed distinct DNA ladders as compared to the control cells AsA- after 24 hr of incubation. Marked cytopathic effects were rather apparent in AsA-treated cells than in control cells AsA- after 24 hr. Our data demonstrate that AsA addition to cell cultures enhances apoptosis induced by M. hyorhinis infection. We suggest that the presence of another external apoptotic pathway by M. hyorhinis infection.

Topics: Apoptosis; Ascorbic Acid; Carcinoma; Cell Line, Tumor; DNA Fragmentation; Dose-Response Relationship, Drug; Humans; Mycoplasma hyorhinis; Stomach Neoplasms

Gastric cancer is a major health burden in the Asia-Pacific region but consensus on prevention strategies has been lacking. We aimed to critically evaluate strategies for preventing gastric cancer.. A multidisciplinary group developed consensus statements using a Delphi approach. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded.. Helicobacter pylori infection is a necessary but not sufficient causal factor for non-cardia gastric adenocarcinoma. A high intake of salt is strongly associated with gastric cancer. Fresh fruits and vegetables are protective but the use of vitamins and other dietary supplements does not prevent gastric cancer. Host-bacterial interaction in H. pylori infection results in different patterns of gastritis and differences in gastric acid secretion which determine disease outcome. A positive family history of gastric cancer is an important risk factor. Low serum pepsinogens reflect gastric atrophy and may be useful as a marker to identify populations at high risk for gastric cancer. H. pylori screening and treatment is a recommended gastric cancer risk reduction strategy in high-risk populations. H. pylori screening and treatment is most effective before atrophic gastritis has developed. It does not exclude the existing practice of gastric cancer surveillance in high-risk populations. In populations at low risk for gastric cancer, H. pylori screening is not recommended. First-line treatment of H. pylori infection should be in accordance with national treatment guidelines.. A strategy of H. pylori screening and eradication in high-risk populations will probably reduce gastric cancer incidence, and based on current evidence is recommended by consensus.

Topics: Adenocarcinoma; Anti-Bacterial Agents; Anticarcinogenic Agents; Ascorbic Acid; Asia; Biomarkers, Tumor; Dietary Supplements; Evidence-Based Medicine; Fruit; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Mass Screening; Pacific Islands; Pedigree; Pepsinogens; Prevalence; Risk Assessment; Risk Factors; Sodium Chloride, Dietary; Stomach Neoplasms; Vegetables; Vitamins

Combination treatment with sodium nitrite (NaNO(2)) and ascorbic acid (AsA) is well known to promote forestomach carcinogenesis in rats and weakly enhance esophageal carcinogenesis under acid reflux conditions. Nitric oxide generation and oxidative DNA damage are considered to be related to the enhancement of carcinogenesis. The purpose of the present study was to investigate whether oxidative DNA damage-associated genotoxicity and tumor initiating potential are involved in the carcinogenesis. In the bacterial reverse mutation assay using Escherichia coli deficient in the mutM gene encoding 8-hydroxydeoxyguanosine (8-OHdG) DNA glycosylase, the combination with NaNO(2) and AsA increased the mutation frequency dramatically, slight increase being evident in the parental strain. In vivo, a significant increase in 8-OHdG levels in the rat forestomach epithelium occurred at 24 h after combined treatment. Six-week-old F344 male rats were given drinking water containing 0.2% NaNO(2) and a diet supplemented with 1% AsA in combination, or the chemicals individually or basal diet alone for 12 weeks. After an interval of 2 weeks, they received 1% butylated hydroxyanisole in the diet for promotion until the end of weeks 52 and 78. Although one squamous cell carcinoma was observed in the combined group, there was no significant variation in tumor development among the groups. The study indicated that the combination of NaNO(2) with AsA induces genotoxicity due to oxidative DNA damage in vitro, and elevates 8-OHdG levels in the forestomach epithelium, but lacks initiating activity in the rat two-stage carcinogenesis model.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Ascorbic Acid; Butylated Hydroxyanisole; Carcinogens; Cocarcinogenesis; Deoxyguanosine; Disease Models, Animal; DNA Damage; DNA, Bacterial; Drug Therapy, Combination; Escherichia coli; Gastric Mucosa; Male; Methylnitronitrosoguanidine; Mutagens; Organisms, Genetically Modified; Oxidation-Reduction; Oxidative Stress; Rats; Rats, Inbred F344; Sodium Nitrite; Stomach Neoplasms

Helicobacter pylori infection induces chronic gastritis and lowers gastric juice ascorbic acid concentrations. We investigated how H. pylori eradication affected multiple variables that could prevent or delay development of new or occult gastric cancer in patients with early gastric cancer treated by endoscopic mucosal resection. Gastric juice pH, nitrite concentrations, and total vitamin C concentrations, serum concentrations of vitamin C and specific H. pylori antibody, and intensity of neutrophil infiltration in gastric mucosa were determined before and after successful H. pylori eradication. Successful eradication increased acid output and ascorbic acid secretion into gastric juice, accompanied by disappearance of polymorphonuclear infiltration from the surface epithelium and decreased gastric juice nitrite concentrations. Our data suggest that H. pylori eradication decreases the nitrosation rate as the ratio of vitamin C to nitrite increases. This decreases reactive oxygen species and nitric oxide, eliminating their damaging effect on DNA and reducing cell turnover.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Female; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Nitrites; Stomach Neoplasms

The objective of this study was to determine whether the intake of nitrate relative to antioxidant vitamin rather than absolute intake of nitrate affects the risk of gastric cancer (GC). In a case-control study in Korea using a food frequency questionnaire, trained dietitians interviewed 136 GC cases and an equal number of controls matched by sex and age. As an index of nitrate intake relative to antioxidant vitamins intake, we calculated the nitrate:antioxidant vitamin consumption ratio. The mean daily nitrate intake from foods was very high in our subjects. Higher absolute intake of nitrate was not associated with GC risk [odds ratios (OR) = 1.13; 95% confidence interval (CI) = 0.42-3.06]. However, the GC risk distinctly increased as the nitrate:antioxidant vitamin consumption ratio increased, particularly with higher nitrate:vitamin E (OR = 2.78; 95% CI = 1.01-7.67) and nitrate:folate ratios (OR = 3.37; 95% CI = 1.28-8.87). Therefore, GC risk was influenced by the intake of nitrate relative to antioxidant vitamins. Our results suggest that a decrease in the intake of nitrate relative to antioxidant vitamins is considerably more effective in reducing GC risk than either a lower absolute intake of nitrate or a higher intake of antioxidant vitamins alone.

Topics: Antioxidants; Ascorbic Acid; Case-Control Studies; Confidence Intervals; Diet; Feeding Behavior; Female; Helicobacter Infections; Helicobacter pylori; Humans; Korea; Male; Middle Aged; Nitrates; Odds Ratio; Risk Factors; Stomach Neoplasms; Surveys and Questionnaires; Vitamin E; Vitamins

P53 codon 72 polymorphisms have been reported to be associated with cancers of the lung, esophagus and cervix. However, there have been no reports on the interaction of select risk factors and p53 codon 72 polymorphisms in gastric cancer susceptibility. 155 gastric cancer cases and 134 cancer-free controls were enrolled at the Memorial Sloan Kettering Cancer Center (MSKCC) from November 1992 to November 1994. The crude odds ratio (OR1) associated with the (Pro/Pro) polymorphism and the risk of gastric cancer was 1.27 (0.70-2.33). Adjusting for age, sex, race and education (OR2) and further adjusting for BMI, calories, sodium, smoking, vitamin C, fiber, alcohol, fat, and H. pylori status (OR3) did not yield significant results. Significant joint effects were associated with high fat consumption (OR1=2.61 (95% CI:1.13-6.06); OR2=2.85 (95% CI:1.14-7.15) for total cancers and for proximal tumors (OR1=2.56 (95%CI:1.00-6.54)). The low vitamin C intake/high-risk polymorphism group (Pro/Pro) had an OR1 of 4.82 (95% CI: 1.72-13.45) and the OR2 was 6.19 (95% CI: 2.08-18.40) for distal tumors. The point estimates were increased for interaction odds ratios but not statistically significant (OR1=4.25 (95% CI: 0.66-27.50); OR2=4.73 (95% CI: 0.67-33.43); OR3=5.55 (95% CI: 0.66-46.47)). Further studies specifically looking at proximal and distal tumors are required to confirm any potential interaction between the p53 codon 72 polymorphisms and environmental risk, in particular low dietary vitamin C and high fat consumption.

Topics: Adult; Aged; Ascorbic Acid; Case-Control Studies; Codon; Energy Intake; Female; Genes, p53; Humans; Male; Middle Aged; Odds Ratio; Polymorphism, Genetic; Risk Factors; Stomach Neoplasms

Dose-dependent promotion effects of combined treatment with sodium nitrite (NaNO2) and ascorbic acid (AsA) on gastric carcinogenesis were examined in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Groups of 15 6-week-old F344 male rats were given 0.01% MNNG in their drinking water for 10 weeks to initiate carcinogenesis in the glandular stomach and a single intragastric administration of 100 mg/kg/bodyweight of MNNG by stomach tube at week 9 to initiate carcinogenesis in the forestomach. From week 11, they received either drinking water containing 0.05, 0.1 or 0.2% NaNO2 and a diet supplemented with 0.1 or 0.2% AsA in combination, each individual chemical alone or a basal diet until the end of week 42. In the forestomach, the incidence of hyperplasia was increased dose dependently by the treatment with NaNO2 alone. Incidences of neoplastic lesions were dramatically increased by the combined treatment with NaNO2 and AsA in a dose-dependent manner, but AsA itself had no effect. In the glandular stomach, only toxicity and regenerative changes were increased by the high-dose combination. In a second short-term experiment conducted for sequential observation, necrosis and strong inflammation were found in the forestomach epithelium shortly after commencing combined treatment with 1.0% AsA and 0.2% NaNO2, followed by hyperplasia, whereas there were no obvious effects in the glandular stomach. In addition, after a 4 h treatment with 1.0% AsA and 0.2% NaNO2, a slight increase in the 8-hydroxy-deoxyguanosine levels in the forestomach epithelium was observed by high-performance liquid chromatography and an electrochemical detection system, albeit without statistical significance. In vitro, electron spin resonance demonstrated nitric oxide formation during incubation with NaNO2 and AsA under acidic conditions. Thus, NaNO2 was demonstrated to exert promoter action in the forestomach, with AsA acting as a strong copromoter through cytotoxicity and regenerative cell proliferation, possibly mediated by oxidative DNA damage, but the combined treatment with NaNO2 and AsA had little influence on glandular stomach carcinogenesis.

Topics: Animals; Ascorbic Acid; DNA Damage; Dose-Response Relationship, Drug; Male; Methylnitronitrosoguanidine; Nitric Oxide; Oxidative Stress; Rats; Rats, Inbred F344; Sodium Nitrite; Stomach Neoplasms

The risk of gastric cancer (GC) associated with dietary intake of nitrosodimethylamine (NDMA) and endogenous formation of nitroso compounds (NOCs) was investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC). The study included 521,457 individuals and 314 incident cases of GC that had occurred after 6.6 average years of follow-up. An index of endogenous NOC (ENOC) formation was estimated using data of the iron content from meat intake and faecal apparent total NOC formation according to previous published studies. Antibodies to Helicobacter pylori and vitamin C levels were measured in a sub-sample of cases and matched controls included in a nested case-control within the cohort. Exposure to NDMA was < 1 microg on average compared with 93 mug on average from ENOC. There was no association between NDMA intake and GC risk (HR, 1.00; 95% CI, 0.7-1.43). ENOC was significantly associated with non-cardia cancer risk (HR, 1.42; 95% CI, 1.14-1.78 for an increase of 40 microg/day) but not with cardia cancer (HR, 0.96; 95% CI, 0.69-1.33). Although the number of not infected cases is low, our data suggest a possible interaction between ENOC and H.pylori infection (P for interaction = 0.09). Moreover, we observed an interaction between plasma vitamin C and ENOC (P < 0.02). ENOC formation may account for our previously reported association between red and processed meat consumption and gastric cancer risk.

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Case-Control Studies; Cattle; Diet; Dimethylnitrosamine; Europe; Female; Helicobacter Infections; Helicobacter pylori; Humans; Iron; Male; Meat; Middle Aged; Nitrosamines; Prospective Studies; Risk Factors; Stomach Neoplasms

Vitamin C is an antioxidant and inhibitor of carcinogenic N-nitroso compound production in the stomach. Higher dietary vitamin C consumption is associated with decreased risk of gastric cancer (GC) in numerous case-control studies, but data from prospective studies are limited, particularly so for blood measures of vitamin C. The objective of this study was to determine the association of plasma and dietary vitamin C levels with the risk of GC in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 European countries. Using a fluorometric method, vitamin C was measured in pre-diagnostic plasma from 215 GC cases (matched controls = 416). Conditional logistic regression models adjusted by body mass index, total energy intake, smoking status/duration/intensity and Helicobacter pylori infection status were used to estimate relative cancer risks. No association with GC risk was observed for dietary vitamin C, whereas an inverse GC risk was observed in the highest versus lowest quartile of plasma vitamin C [odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.31-0.97, P(trend) = 0.043], which was maintained after exclusion of cases with

Topics: Aged; Ascorbic Acid; Case-Control Studies; Cohort Studies; Dietary Supplements; Europe; Female; Helicobacter pylori; Humans; Incidence; Logistic Models; Male; Middle Aged; Prospective Studies; Stomach Neoplasms

We quantified the effect of antioxidant vitamins in gastric cancer risk, taking into account Helicobacter pylori seropositivity and overall fruit and vegetable intake. Incident cases were identified in two large hospitals in Porto, Portugal, and controls were randomly sampled among city dwellers. Food intake was assessed with a previously validated semiquantitative food-frequency questionnaire. A commercially available chromatographic immunoassay was used for the detection of immunoglobulin G antibodies. Complete questionnaire information and serum samples were available for 233 cases and 311 controls. Compared with subjects in the lowest tertile of dietary intake, the odds ratios (ORs) for those in the highest were 0.85 (95% confidence interval, CI = 0.45-1.60) for vitamin C, 1.04 (95% CI = 0.60-1.80) for vitamin E, and 1.33 (95% CI = 0.77-2.30) for provitamin A carotenoids after further adjusting for fruit and vegetable consumption. Fruit and vegetables remained an independent protective factor (OR = 0.45; 95% CI = 0.23-0.89) after further adjustment for the intake of antioxidant vitamins. H. pylori status had no significant interaction with dietary items. Factors other than H. pylori infection and intake of vitamin C and provitamin A carotenoids seem to account for the inverse association between fruit and vegetable consumption and gastric cancer.

Topics: Aged; Antioxidants; Ascorbic Acid; Case-Control Studies; Confidence Intervals; Diet; Diet Surveys; Female; Fruit; Helicobacter Infections; Helicobacter pylori; Humans; Immunoglobulin G; Male; Middle Aged; Odds Ratio; Portugal; Risk Factors; Stomach Neoplasms; Surveys and Questionnaires; Vegetables; Vitamin E; Vitamins

To find out the mechanisms of redifferentiation and reversion of malignant human gastric cancer cells induced by ascorbic acid.. Human gastric cancer cells grown in the laboratory were used. The Trypan blue dye exclusion method was used to determine the cell doubling time. The electrophoresis rate and colonogenic potential were the indices used to measure the rate of redifferentiation. The content of malondialdehyde (MDA) was measured using the thiobarbituric acid (TBA) method. The activities of superoxide dismutase (SOD), catalase (CAT) and the content of H202 were evaluated by spectrophotography.. Six mmol/L ascorbic acid was used as a positive control. Human gastric cancer cells were treated with 75 microm hydrogen peroxide, which alleviated many of the malignant characteristics. For example, the cell surface charge obviously decreased and the electrophoresis rate dropped from 2.21 to 1.10 microm x s(-1) x V(-1) x cm(-1). The colonogenic potential, a measure of cell differentiation, decreased 90.2%. After treatment with ascorbic acid, there was a concentration- and time-dependent increase in hydrogen peroxide (H202) and the activity of superoxide dismutase (SOD). However, the activity of catalase (CAT) resulted in a concentration- and time-dependent decrease. SOD and 3-amino-1,2,4-triazole (AT) exhibited some effects, but there were statistically significant differences between the SOD and AT group and the H202 group.. Ascorbic acid induces growth inhibition and redifferentiation of human gastric cancer cells through the production of hydrogen peroxide.

Topics: Antioxidants; Ascorbic Acid; Cell Differentiation; Humans; Hydrogen Peroxide; Stomach Neoplasms; Tumor Cells, Cultured

Epidemiological studies show that high intake of food-bound vitamin C and E reduces the risk of gastric cancer. Whether dietary supplementation with antioxidant micronutrients interferes with Helicobacter pylori infection and associated diseases is unclear. The aim of this study was to investigate if dietary vitamin C or E supplementation influences the progression of gastritis, gastric mucosal nitrosative and oxidative protein damage, gastric mucosal lipid peroxidation, or gastric mucosal oxidative DNA damage in H. pylori-infected Mongolian gerbils.. Gerbils were divided into four groups: H. pylori-infected animals fed with vitamin C- or vitamin E-supplemented food, and infected and uninfected animals given standard rodent food. Subgroups of animals were killed at different time-points until 52 weeks postinfection. Concentrations of 3-nitrotyrosine and thiobarbituric acid-reactive substances (TBARS) in the gastric mucosa were determined with an immunodot blot and a fluorometric method, respectively. Mucosal concentrations of carbonyl carbons on proteins and 8-hydroxydeoxyguanosine were determined by enzyme-linked immunosorbent assay. Gastritis was scored semiquantitatively.. Vitamin supplements had no effect on the colonization with H. pylori. Vitamin C as well as vitamin E supplements reduced mucosal 3-nitrotyrosine concentrations to normal levels in infected animals. Vitamin E supplements decreased mucosal protein carbonyls and TBARS in short-term gastritis. In addition, vitamin C supplements caused attenuated mucosal oxidative DNA damage and milder mucosal inflammation in short-term gastritis.. Vitamin C or vitamin E supplementation leads to some short-term protective effects on H. pylori-induced gastritis in Mongolian gerbils. These effects seem to subside over time when the infection persists.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Ascorbic Acid; Deoxyguanosine; Dietary Supplements; Disease Models, Animal; Gastric Mucosa; Gastritis; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Male; Stomach Neoplasms; Thiobarbituric Acid Reactive Substances; Tyrosine; Vitamin E; Vitamins

Cyclooxygenase 2 (COX-2) is induced by the presence of Helicobacter pylori (H. pylori) on the gastric mucosa as part of the inflammatory response; this results in the synthesis of prostaglandins that amplify the local inflammatory response. The presence of H. pylori inhibits the secretion of ascorbate into the gastric lumen. Interestingly, ascorbate inhibits the growth of H. pylori and low dietary levels are associated with an increased risk of gastric adenocarcinoma. We therefore investigated the effect of ascorbate on H. pylori mediated COX-2 induction and prostaglandin production in vitro.. H. pylori was cocultured with gastric epithelial cells in the presence of ascorbate at physiological concentrations. The expression of COX-2 was assessed by Western blotting and prostaglandin E(2) (PGE(2)) was assessed by ELISA.. Ascorbate inhibited gastric cell PGE(2) synthesis but not in COX-2 expression in response to H. pylori. In the absence of the organism, ascorbate also reduced PGE(2) expression in cells that constitutively express COX-2, again with no reduction of COX-2 protein expression.. Physiological concentrations of ascorbate inhibit PGE(2) but not COX-2 expression in response to H. pylori in gastric epithelial cells.

Topics: Antioxidants; Ascorbic Acid; Blotting, Western; Cell Line; Cell Line, Tumor; Cyclooxygenase 2; Dinoprostone; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Gastric Mucosa; Helicobacter pylori; Humans; Membrane Proteins; Prostaglandin-Endoperoxide Synthases; Stomach Neoplasms

A hospital-based case-control study of 295 cases with histologically confirmed gastric cancer and age and sex-matched controls was conducted to evaluate the effect of dietary vitamin C intake upon the relation between Helicobacter pylori infection and gastric cancer in Korea in 1997-1998. Anti-H. pylori IgG was detected by ELISA. A food frequency questionnaire, and a questionnaire on demographic factors, including past medical history, smoking, alcohol consumption, and life style was also administered. The prevalences of H. pylori IgG in cases and controls were 80.7% and 71.2%, respectively, and the odds ratio (OR) of H. pylori for gastric cancer was 1.68 (95% confidence interval (CI): 1.14, 2.44), after adjusting for age, sex, educational level, and a past medical history of gastritis or gastric ulcer. In a stratified analysis, H. pylori seropositivity was found to be a significant risk factor for gastric cancer in the low vitamin C intake group (OR = 4.68; 95% CI: 1.97, 11.1), but not in the high vitamin C intake group (OR = 0.72; 95% CI: 0.32, 1.65). Vitamin C intake was found to modify the relation between H. pylori and gastric cancer.

Topics: Adult; Ascorbic Acid; Case-Control Studies; Female; Helicobacter pylori; Humans; Immunoglobulin G; Korea; Male; Middle Aged; Seroepidemiologic Studies; Stomach Neoplasms; Surveys and Questionnaires

Researches show that epidemiologic factors of gastric cancer include living habit, eating moldy food and pickles, dystrophy, lack of microelements, and inherit, etc. This study was to explore universalities of these factors in Wuwei, a city in northwest China with high incidence of gastric cancer, and provide evidences for the first-prevention of gastric cancer.. Family histories of the residents in Wuwei City were investigated with case-control method. Separating ratio and heredity degree of gastric cancer were calculated with Li-Mantel-Cart method and Falconer's regression method. Chronic gastritis patients were followed-up by home-visit, gastroscopy, and pathology. Cancerigenic fungi and volatility N-nitrosate compounds in residents' meal, Helicobacter pylori (Hp) in gastric mucosa, and total content of vitamin C in 293 healthy adults' serum were detected by culture, authentication, and laboratory examinations.. In Wuwei City, the separating ratio of gastric cancer was 0.077; the heredity degree of first-degree relatives was 22.91%u cancerization rate of year in person of atrophic gastritis crowd was 1.09%. Eight kinds of nitrosamine and 14 kinds of cancerigenic fungi were detected from residents' meal. Total content of vitamin C in serum of the 293 healthy adults in summer was (5.74+2.79) mg/L. Positive rate of Hp in gastric mucosa of the residents was 67%.. The major extrinsic factors of gastric cancer in Wuwei City include various strong carcinogens existing in residents' meal and lack of vitamin Cu its intrinsic factors include infection of Hp, atrophic gastritis (especially atypical hyperplasia), and heritage susceptibility.

Topics: Adult; Ascorbic Acid; China; Disease Progression; Female; Follow-Up Studies; Food Analysis; Food Microbiology; Gastric Mucosa; Gastritis, Atrophic; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Nitrosamines; Precancerous Conditions; Risk Factors; Stomach Neoplasms

To examine the effects of dietary factor and Helicobacter pylori (H. pylori) infection with emphasis on vitamin intake on the risk of gastric cancer (GC), we conducted a case-control study in South Korea, a high-risk area for GC. Trained dietitians interviewed 136 cases histologically diagnosed with GC. An equal number of hospital controls was selected by matching sex and age. High dietary intakes of vegetable fat [odds ratio (OR) = 0.35; 95% confidence interval (CI) = 0.15-0.83], folate (OR = 0.35; 95% CI = 0.13-0.96), and antioxidants, such as vitamin A (OR = 0.34; 95% CI = 0.13-0.83), beta-carotene (OR = 0.33; 95% CI = 0.13-0.82), vitamin C (OR = 0.26; 95% CI = 0.09-0.72), and vitamin E (OR = 0.41; 95% CI = 0.17-1.01), were shown to have a protective effect on GC risk using a multivariate model adjusting for foods significantly related to GC in our previous study (charcoal grilled beef, spinach, garlic, mushroom, and a number of types of kimchi) and supplement use. When stratified according to H. pylori infection, high intakes of vitamin C (OR = 0.10; 95% CI = 0.02-0.63) and vitamin E (OR = 0.16; 95% CI = 0.03-0.83) exhibited highly significant inverse associations with GC among the H. pylori-infected subjects compared with noninfected individuals. GC risk was significantly decreased only when consumption levels for two of these vitamins were high. Our findings suggest that high intake of antioxidant vitamins contribute to the reduction of GC risk and that GC risk in Korea may be decreased by encouraging those with H. pylori infection to increase their intake of antioxidant vitamins.

Topics: Antioxidants; Ascorbic Acid; Case-Control Studies; Feeding Behavior; Female; Helicobacter Infections; Helicobacter pylori; Humans; Korea; Male; Middle Aged; Multivariate Analysis; Stomach Neoplasms; Surveys and Questionnaires; Vegetables; Vitamin E

To examine the role of six flavonoid classes (flavanones, flavan-3-ols, flavonols, flavones, anthocyanidins and isoflavones) and vitamin C in the aetiology of stomach cancer.. Case-control study undertaken in Greece in the 1980s. Dietary information was obtained from 110 patients with incident stomach adenocarcinoma and 100 control patients. Flavonoid estimates were based on the recently released database of the US Department of Agriculture.. In models including sociodemographic variables, energy intake, vegetables, fruits and, alternatively, vitamin C the six flavonoid classes, only flavanones and vegetables remained significantly inversely associated with stomach cancer risk. The odds ratio (95% confidence intervals) per one standard deviation increase of intake of flavanones was 0.55 (0.31-0.96) whereas for vitamin C it was 1.05 (0.46-2.41). When fruits and vegetables were not adjusted for, both vitamin C and several flavonoid categories were inversely associated with stomach cancer risk, but these associations could be attributed to other compounds in these foods.. Among the major flavonoid classes studied, only flavanone intake is inversely associated with stomach cancer risk and could account for the apparent protective effect of fruit intake against this form of cancer. Additional factors, however, are likely to be involved in the consistent protection conveyed by vegetables.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Case-Control Studies; Diet; Female; Flavanones; Flavonoids; Fruit; Humans; Male; Middle Aged; Odds Ratio; Stomach Neoplasms; Vegetables

Some of the world's highest rates of stomach cancer are found in Poland. Reasons for the increased incidence are not known, but high intake of sausages and other preserved foods and low intake of fresh fruits and vegetables may be involved. A case-control study comprising residents newly diagnosed with stomach cancer during 1994-96 and controls randomly selected from the general population was conducted in Warsaw, Poland. Standardized interviews were conducted to ascertain usual consumption of 118 common foods and beverages and other exposures. Using data from direct interviews with 274 cases and 463 controls, odds ratios of stomach cancer were calculated as estimates of risks associated with dietary factors, adjusting for age, sex, education, smoking, and caloric intake. Risk of stomach cancer was inversely related to intake of total fruits and dark green-yellow vegetables and to indices of vitamins C and E and alpha- and beta-carotenes. However, risk was not significantly increased among those with high intake of pickled/salted vegetables and sausages. Risks were positively associated with increased intake of breads/cereals/rice/pasta and other refined grains, as well as a high carbohydrate index. Our findings add to the evidence of a protective effect of fruits and certain vegetables on stomach cancer risk, but do not indicate that high intake of sausage and other preserved foods typical in the Polish diet has contributed to the country's elevated stomach cancer incidence. Our data also suggest that high carbohydrate consumption may influence risk, but further confirmation is needed.

Topics: Aged; Ascorbic Acid; Carotenoids; Case-Control Studies; Diet; Diet Surveys; Dietary Carbohydrates; Dietary Fiber; Female; Fruit; Humans; Interviews as Topic; Male; Middle Aged; Odds Ratio; Poland; Risk; Smoking; Stomach Neoplasms; Surveys and Questionnaires; Vegetables

A hospital-based case-control study was carried out between 1994 and 1996 to evaluate the risk of gastric cancer (GC) according to Helicobacter pylori-CagA (+) seropositivity, nitrite and ascorbic acid intake. Three geographical areas of Mexico were selected on the basis of their contrasting dietary patterns and H. pylori seroprevalence. Nitrite and ascorbic acid consumption were estimated by interview among 211 cases and 454 matched controls. Serum antibodies against IgG H. pylori and CagA were detected by immunosorbent assays. The adjusted risk for GC was significantly higher among CagA+ subjects compared with those that were CagA negative (Odds Ratio (OR)=2.04 95% Confidence Interval (CI) 1.37-3.02 P for trend P < 0.001), this effect remained significant among diffuse GC cases (OR 2.05 95% CI 1.25-3-36). No significant effects due to nitrite and ascorbic consumption or interactions of these nutrients with CagA seropositivity were detected. Seropositivity to H. pylori CagA+ strains may be an independent factor for diffuse GC in Mexico.

Topics: Adult; Aged; Aged, 80 and over; Antigens, Bacterial; Ascorbic Acid; Bacterial Proteins; Biomarkers, Tumor; Case-Control Studies; Diet; Enzyme-Linked Immunosorbent Assay; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Nitrites; Risk Factors; Stomach Neoplasms

Data on blood levels of specific carotenoids and vitamins in relation to gastric cancer are scarce. Little is known about the relationship between prediagnostic serum levels of carotenoids other than beta-carotene and risk of gastric cancer especially in non-Western populations. Prediagnostic serum concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein/zeaxanthin, retinol, alpha-tocopherol, gamma-tocopherol, and vitamin C were determined on 191 cases and 570 matched controls within a cohort of 18,244 middle-aged or older men in Shanghai, China, with a follow-up of 12 years. High serum levels of alpha-carotene, beta-carotene, and lycopene were significantly associated with reduced risk of developing gastric cancer (all Ps for trend /=3 drinks of alcohol per day; the odds ratios (95% confidence intervals) for the second, third, and fourth quartile categories were 0.69 (0.28-1.70), 0.36 (0.14-0.94), and 0.39 (0.15-0.98), respectively, compared with the lowest quartile of vitamin C (P for trend = 0.02). There were no statistically significant relationships of serum levels of beta-cryptoxanthin, lutein/zeaxanthin, retinol, alpha-tocopherol, and gamma-tocopherol with gastric cancer risk. The present study implicates that dietary carotenes, lycopene, and vitamin C are potential chemopreventive agents for gastric cancer in humans.

Topics: Alcohol Drinking; Antioxidants; Ascorbic Acid; Carotenoids; Case-Control Studies; China; Humans; Male; Micronutrients; Middle Aged; Risk Factors; Smoking; Stomach Neoplasms; Tocopherols

Topics: Ascorbic Acid; Case-Control Studies; Dose-Response Relationship, Drug; Helicobacter Infections; Humans; Risk Factors; Stomach Neoplasms

Oxidative stress participates in the cell carcinogenesis by inducing DNA mutations. Our aim was to assess whether ascorbic acid, an antioxidant, could have a role in preventing ROS (Reactive Oxygen Species) generation in experimental gastric carcinoma in a rat model.. Experimental gastric cancer was induced in twelve Wistar male rats (weighting 250-350 g) by profound duodeno-gastric reflux throught split gastrojenunostomy. The rats were allocated to the following groups: Group I (n=6) was the control; Group II (n=6) which was mantained with daily intake of tape water with Vitamin C (30 mg/Kg). After 6 or 12 months, samples of gastric tumor or non tumor mucosa were taken from the anastomosis of both groups. Oxidative stress was measured by superoxide quantification through lucigenin-amplified chemiluminescence base and by staining with Nitrobluetetrazolium. The histopathologic confirmation of adenocarcinoma was made by eosin-hemathoxilin method.. The intestinal type of gastric adenocarcinoma was microscopically identified in all animals of group I whereas only 3 rats of group II showed an adenocarcinoma without macroscopic evidence of them. The cancers were located in the anastomosis in all cases. Basal luminescence from tumor gastric tissue generated 38.4+/-6.8 count per minute/mg/X10(6) (mean+/-SD) and 14.9+/-4.0 count per minute/mg/X10(6), respectively, in group I and II animals (P<0.05). The Nitrobluetetrazolium method showed intense staining in tumor tissues but not in non neoplasic mucosa.. Experimental gastric tumors seem to produce more reactive oxygen species than non neoplasic gastric tissue. The reduction of oxidative stress and gastric tumor incidence in rats were induced by the intake of ascorbic acid. Therefore, it may have a role in the prevention of gastric carcinoma.

Topics: Animals; Antioxidants; Ascorbic Acid; Male; Oxidative Stress; Rats; Rats, Wistar; Stomach Neoplasms

Serum superoxide dismutase, plasma ascorbic acid and lipid peroxidation in H. pylori gastritis and gastric cancer patients were compared with values for age matched healthy subjects. Serum superoxide dismutase and serum malondialdehyde were analyzed spectrophotometrically whereas plasma ascorbic acid was determined by colorimetric method. Significant increase in serum superoxide dismutase and serum malondialdehyde and significant decrease in plasma ascorbic acid were observed in H. pylori gastritis and gastric cancer patients compared to control subjects. The concentration of serum superoxide dismutase and serum malondialdehyde was significantly higher and plasma ascorbic acid was significantly lower in gastric cancer as compared to H. pylori gastritis patients. Our results demonstrate that a correlation existed between the concentration of serum superoxide dismutase, plasma ascorbic acid and lipid peroxidation in H. pylori gastritis and gastric cancer patients.

Topics: Adult; Antioxidants; Ascorbic Acid; Female; Gastritis; Helicobacter Infections; Humans; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Oxidants; Oxidative Stress; Stomach Neoplasms; Superoxide Dismutase

N-nitroso compounds are carcinogens formed from nitrite, a process that is inhibited by vitamin C in gastric juice. Helicobacter pylori infection has been reported to increase nitrite and decrease vitamin C in gastric juice. Therefore, susceptibility to gastric cancer in H. pylori-infected patients may be derived from increased N-nitroso compounds in gastric juice. However, most H. pylori-infected patients do not develop gastric cancer.. To investigate additional factors that may affect susceptibility to gastric cancer, we compared nitrite and vitamin C levels in gastric juice from H. pylori-infected patients with and without gastric cancer.. Serum and gastric juice were obtained from 95 patients undergoing diagnostic endoscopy, including those with normal findings, duodenal ulcer, gastric ulcer, atrophic gastritis and gastric cancer. Serum was analysed for H. pylori antibody, nitrate and nitrite, gastrin and pepsinogens; gastric juice was analysed for pH, nitrite and vitamin C.. pH and nitrite levels were increased and vitamin C levels decreased in the gastric juice of patients with atrophic gastritis and gastric cancer compared with other patients. However, in patients with a similar gastric acidity (pH 5-8), nitrite concentrations in the gastric juice were significantly higher and vitamin C levels significantly lower in patients with gastric cancer than in those with atrophic gastritis.. Although hypochlorhydria increases intraluminal nitrite and decreases intraluminal vitamin C, which increases the intraluminal formation of N-nitroso compounds, our results indicate that patients with gastric cancer may have additional factors that emphasize these changes.

Topics: Aged; Ascorbic Acid; Female; Gastric Juice; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Nitrites; Risk Factors; Stomach Neoplasms

High luminal concentrations of nitric oxide are generated at the human gastro-oesophaegal junction and within Barrett's oesophagus due to the reduction of salivary nitrite to nitric oxide by acidic gastric juice. Salivary nitrite is derived from the entero-salivary recirculation of dietary nitrate. Our aim was to determine whether nitric oxide generated within the lumen will exert nitrosative stress on the adjacent epithelium. A benchtop model was constructed reproducing the nitrite chemistry occurring within the lumen of the upper gastrointestinal tract where saliva encounters acidic gastric juice. It incorporated an epithelial compartment maintained at pH 7.4 and separated from the lumen by a hydrophobic barrier with the properties of the epithelial lipid cell membrane. The secondary amine morpholine was used to measure N-nitroso compound formation in both the lumen and epithelial compartment. Adding 100 micro M nitrite to the acidic (pH 1.5) luminal compartment depleted of ascorbic acid generated 6.2 +/- 2.0 micro M (mean +/- SE) N-nitrosomorpholine in that compartment and 2.2 +/- 0.1 micro M nitrosomorpholine in the epithelial compartment at 30 min. When 100 micro M nitrite was added to the acidic luminal compartment containing physiological concentrations of ascorbic acid, all the nitrite was immediately converted to nitric oxide and no N-nitrosomorpholine was formed within that compartment. However, the nitric oxide rapidly diffused from the luminal compartment into the epithelial compartment and there generated very high concentrations of N-nitrosomorpholine (137 +/- 5.6 micro M at 30 min). The addition of ascorbic acid or glutathione to the epithelial compartment could only reduce nitric oxide-induced nitrosation within that compartment by 40%. The nitrate-derived nitric oxide generated within the lumen where saliva encounters gastric acid is likely to exert substantial nitrosative stress on the adjacent epithelium. This may contribute to the high prevalence of mutagenesis at this anatomical site.

Topics: Ascorbic Acid; Cell Membrane; Diet; Dose-Response Relationship, Drug; Epithelium; Esophageal Neoplasms; Glutathione; Humans; Hydrogen-Ion Concentration; Models, Biological; Morphine; Mutagenesis; Nitrates; Nitric Oxide; Nitrites; Nitrogen; Saliva; Stomach Neoplasms; Stress, Physiological; Time Factors

Free oxygen radicals contribute to gastric mucosal damage induced by acetylic-salicylic acid (ASA). Vitamin C has been shown to reduce gastric toxicity of ASA in humans. We intended to assess the role of heme oxygenase-1 (HO-1) in this process by application of these substances to AGS and KATO III cells. HO-1 expression was monitored by real-time RT-PCR, Western blot, and HO activity measurement. HO-1 mRNA was significantly elevated by either ASA or vitamin C in gastric epithelial cells, combination of both substances further increased expression. HO-1 protein and enzyme activity rose in cells exposed to vitamin C alone or combined with ASA, but not after stimulation with ASA alone. In contrast to endothelia, in which ASA simultaneously induces HO-1 mRNA and protein expression, gastric epithelial cells require vitamin C to translate HO-1 mRNA into active protein, which then may exert gastroprotection by its antioxidant and vasodilative properties.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Aspirin; Cell Line, Tumor; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Gastric Mucosa; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Humans; Membrane Proteins; Stomach Neoplasms

Topics: Antioxidants; Ascorbic Acid; Case-Control Studies; China; Dietary Fats; Dietary Proteins; Eating; Female; Humans; Male; Micronutrients; Multivariate Analysis; Risk Factors; Stomach Neoplasms; Vitamin A

The effects of lycopene on blood oxidant-antioxidant balance during N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in the presence of saturated sodium chloride (S-NaCl) as promoting agent were investigated. Enhanced lipid peroxidation in the blood of tumour-bearing animals was accompanied by significant decreases in the levels of reduced glutathione (GSH), ascorbic acid and vitamin E and the activities of glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR). Administration of lycopene significantly lowered the concentrations of lipid peroxides and enhanced antioxidant levels. We suggest that the modulatory effects of lycopene on the blood oxidant-antioxidant balance may be responsible for its chemopreventive potential.

Topics: Animals; Ascorbic Acid; Body Weight; Carotenoids; Erythrocytes; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Lipid Peroxidation; Lycopene; Male; Methylnitronitrosoguanidine; Neoplasms, Experimental; Rats; Rats, Wistar; Sodium Chloride; Stomach Neoplasms; Thiobarbituric Acid Reactive Substances; Vitamin E

To explore the effects and mechanisms of ascorbic acid (AA) and sodium selenite (SS) on growth inhibition and redifferentiation in human gastric cancer cells.. In the present study, trypan blue dye exclusion method was used to determine the cell growth curve and mitotic index, cell electrophoresis and colonogenic potential were used as the indexes of redifferentiation. In order to find out the mechanisms of redifferentiation, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were assayed, the content of malondialdehyde (MDA), reduced glutathione (GSH) and H2O2 were evaluated.. After treatment with AA 3 mol/L + SS 2 mu mol/L, the growth rate and mitotic index of human gastric cancer cells (MGc-803) decreased remarkably. The indexes related with cell malignancy were alleviated. For example, cell surface charge was obviously decreased, the electrophoresis rate was dropped from 2.21 to 1.15 mu m.s-1.V-1.cm-1. The indexes related with cell redifferentiation were promoted. For example, the colonogenic potential was decreased to 93.5%. These results indicated that redifferentiation of human gastric cancer cells was successfully induced by AA + SS. The activities of SOD and GPX were significantly higher, while the activity of CAT was slower in treated group than that in the control. The content of MDA was slightly decreased, GSH was sharply decreased, and H2O2 content was dramatically increased.. These results indicated that combination of ascorbic acid and sodium selenite may induce the redifferentiation of human gastric cancer cells and inhibit cell growth by virtue of enhancing the activities of antioxidative enzymes and inducing the formation of H2O2, and altering the cell redox status. Combination of ascorbic acid and sodium selenite may be a potent anticancer agent for human gastric cancer.

Topics: Antioxidants; Ascorbic Acid; Catalase; Cell Differentiation; Glutathione Peroxidase; Humans; Mitotic Index; Sodium Selenite; Stomach Neoplasms; Superoxide Dismutase; Tumor Cells, Cultured

Gastric juice vitamin C may be protective against gastric carcinogenesis but concentrations are significantly reduced by Helicobacter pylori infection. We investigated the in vitro effects of vitamin C at concentrations comparable with those found in gastric juice on gastric cancer cells and H pylori.. Gastric cancer cell lines and various H pylori strains were treated with L-ascorbic acid for up to 72 hours. Cell viability, and protein and DNA synthesis were determined. Flow cytometry was used for assessment of H pylori adherence, cell cycle distribution, and apoptosis. H pylori growth and its haemagglutination activity were determined using viability count and microtitration assay.. Vitamin C induced a significant dose dependent growth inhibition of gastric AGS and MKN45 cells but this effect was significantly reduced at levels similar to those in gastric juice of H pylori infected patients (<50 microM). Although vitamin C had no obvious effect on H pylori growth, haemagglutination activity, or adherence ability to gastric AGS cells compared with untreated controls, it significantly enhanced H pylori associated apoptosis and induced cell cycle arrest in these cells.. Vitamin C may inhibit gastric cancer cell growth and alter H pylori induced cell cycle events at concentrations comparable with those in gastric juice, but has no effect on H pylori growth or pathogenicity. However, the inhibitory effect on gastric cancer cells was lost at vitamin C concentrations found in patients with H pylori infection.

Topics: Adenocarcinoma; Ascorbic Acid; Bacterial Adhesion; Cell Division; Flow Cytometry; Gastric Juice; Helicobacter Infections; Helicobacter pylori; Hemagglutination; Hemagglutination Tests; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa; Stomach Neoplasms; Tumor Cells, Cultured

Supplementation with antioxidant vitamins has been associated with decreased risk of stomach cancer or regression of precancerous lesions in high-risk areas of China and Colombia. We examined the association between stomach cancer mortality and regular use (> or =15 times per month) of individual vitamin C supplements, individual vitamin E supplements, and multivitamins among 1,045,923 United States adults in the Cancer Prevention Study II (CPS-II) cohort. CPS-II participants completed a questionnaire at enrollment in 1982 and were followed for mortality through 1998. During follow-up, there were 1,725 stomach cancer deaths (1,127 in men and 598 in women). After adjustment for multiple potential stomach cancer risk factors, vitamin C use at enrollment was associated with reduced risk of stomach cancer mortality [rate ratio (RR), 0.83; 95% confidence interval (CI), 0.68-1.01]. However, this reduction in risk was observed only among participants with short duration use at enrollment (RR, 0.68; 95% CI, 0.51-0.91 for <10 years of use; RR, 1.00; 95% CI, 0.73-1.38 for > or =10 years of use). There was no association between stomach cancer mortality and regular use of vitamin E (RR, 1.02; 95% CI, 0.82-1.27) or multivitamins (RR, 0.89; 95% CI, 0.77-1.03), regardless of duration of use. Our results suggest that the use of vitamin C, vitamin E, or multivitamin supplements may not substantially reduce risk of stomach cancer mortality in North American populations in which stomach cancer rates are relatively low. Our results do not rule out effects of vitamin supplementation in areas in which stomach cancer rates are high and stomach cancer etiology may differ.

Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Ascorbic Acid; Cohort Studies; Dietary Supplements; Female; Humans; Male; Middle Aged; Primary Prevention; Proportional Hazards Models; Risk Factors; Sex Distribution; Stomach Neoplasms; Survival Analysis; Survival Rate; United States; Vitamin E

The aim of the study was to elucidate what are the concentrations of vitamin C in gastric juice in patients with gastric cancer in comparison to patients with metaplasia.. In patients aged 20 to 75 years with H. pylori infection and chronic gastritis, metaplasia and gastric cancer the concentration of vitamin C was determined by spectrofotometry of gastric juice during gastroscopy. On the basis of the results of histological examination the following four groups were isolated. Group I (control)--12 patients with normal gastric mucosa, group II--15 patients with chronic gastritis, group III--17 patients with metaplasia and group IV--16 patients with gastric cancer H. pylori infection was confirmed by urease test and histological examination (Giemsa stainning) in all patients.. In controls the mean concentration of vitamin C in gastric juice was 18.2 mg/ml (5.7-31.2 mg/ml), in group II--6.3 mg/ml (2.9-13.1 mg/ml) in group III--3.9 mg/ml (2.6-10.1 mg/ml) and group IV--3.2 mg/ml (1.7-9.2 mg/ml). Statistically significant differences of vitamin C concentration were found among group I and group II, III and IV (p<0.001) and among groups II and III and IV (p < 0.01).. There are not differences of vitamin C concentration in gastric juice between patients with metaplasia and patients with gastric cancer. This points out that low levels of this vitamin in gastric juice might play the role in the earlier stages of carcinogenesis.

Topics: Adult; Ascorbic Acid; Female; Gastric Juice; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Precancerous Conditions; Stomach Neoplasms

Topics: Anti-Bacterial Agents; Antioxidants; Ascorbic Acid; beta Carotene; Dietary Supplements; Disease Progression; Helicobacter Infections; Helicobacter pylori; Humans; Randomized Controlled Trials as Topic; Stomach; Stomach Neoplasms; Treatment Outcome

Topics: Achlorhydria; Ascorbic Acid; beta Carotene; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Phenotype; Precancerous Conditions; Remission Induction; Stomach Neoplasms; Treatment Outcome

Numerous components of fruit and vegetables are considered to decrease the risk of gastric carcinoma. In the current prospective study, the authors examined the association between the intake of vitamins, carotenoids, and dietary fiber and vitamin supplement use and the incidence rate of gastric carcinoma.. The Netherlands Cohort Study began in 1986 with 120,852 men and women ages 55-69 years. Data regarding diet and other covariates were collected by means of a self-administered questionnaire. After 6.3 years of follow-up, data regarding 282 incident cases of gastric carcinoma and 3123 subcohort members were available for case-cohort analyses.. In analyses adjusted for age, gender, smoking history, education, stomach disorders, and family history of gastric carcinoma, an inverse association with vitamin C intake (relative risk [RR] for highest vs. lowest intake category, 0.7; 95% confidence interval [95% CI], 0.5-1.0) was observed, with a borderline significant trend across three intake categories (P = 0. 06). After the exclusion of cases diagnosed in the first and second follow-up years, the RR was 0.9 (95% CI, 0.6-1.2; P trend = 0.44). Intake of retinol and beta-carotene were associated positively with gastric carcinoma risk with highest versus lowest quintile RRs of 1. 6 (95% CI, 1.0-2.5; P trend = 0.02) and 1.6 (95% CI, 1.0-2.6; P trend = 0.13), respectively, after the exclusion of first-year and second-year cases. Intake of folate, vitamin E, alpha-carotene, lutein plus zeaxanthin, beta-cryptoxanthin, lycopene, and dietary fiber was not associated with gastric carcinoma. Patients who used vitamin A-containing supplements had a lower risk of gastric carcinoma than nonusers (RR = 0.4; 95% CI, 0.2-0.9).. No clear inverse associations were found between the intake of vitamins, carotenoids, and dietary fiber and the risk of gastric carcinoma after adjustment for confounding variables and the exclusion of first-year and second-year cases.

Topics: Aged; Anticarcinogenic Agents; Ascorbic Acid; Carotenoids; Cohort Studies; Dietary Fiber; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Netherlands; Prospective Studies; Risk Factors; Stomach Neoplasms; Surveys and Questionnaires; Vitamin A; Vitamin E; Vitamins

In spite of diverging incidence trends, subsite, and subtype-specific gastric cancer data on the association with dietary antioxidants are sparse. We aimed to test whether the apparent protective effect of antioxidants is mainly confined to noncardia (distal) cancer of the intestinal subtype, to which most of the incidence decline in gastric cancer has been ascribed. In a Swedish study base (total population 1.3 million), we interviewed 567 cases uniformly classified to subsite (cardia vs. noncardia) and subtype (intestinal vs. diffuse), and 1165 population-based controls, frequency matched for age and sex. Serologic data on H. pylori status was available for a subset of 542 individuals. Ascorbic acid (vitamin C) was inversely associated with all subsites and subtypes of gastric cancer in a significant dose-response manner (all p<0.05), with risk reductions between 40% and 60%. beta-carotene was also strongly and negatively associated with risk, particularly with the intestinal type. The associations with alpha-tocopherol (vitamin E) were less clear. The highest parallel intake of all three antioxidants (quartiles 4), compared to those with the lowest parallel intakes (quartiles 1), was associated with a 70% lower risk of developing noncardia cancer (OR 0.3, 95% CI 0.1-0.9). Our results suggest that antioxidants might be especially beneficial among subjects at increased risk for gastric cancer such as smokers and those infected by H. pylori. We conclude that a high intake of antioxidants, as a consequence of high consumption of fruit and vegetables, may lower the risk not only for gastric cancer of the intestinal type, but also for diffuse type adenocarcinoma and cardia cancer.

Topics: Adenocarcinoma; Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cardia; Case-Control Studies; Female; Fruit; Helicobacter pylori; Humans; Intestinal Neoplasms; Male; Middle Aged; Odds Ratio; Risk Factors; Smoking; Stomach Neoplasms; Sweden; Vegetables; Vitamin E

A long-term sufficient intake of fruits and vegetables reduces significantly the risk of gastric and colorectal carcinoma. It is anticipated that natural antioxidants are involved in this effect in addition to other substances. The aim of this study was to determine levels of vitamins A, C and E, as well as beta-carotene, selenium, zinc and copper in blood of 249 patients with precancerous lesions (atrophic gastritis, gastric hyperplastic polyp, gastric, colonic and rectal adenoma, chronic ulcerative colitis) and in 96 individuals with gastric, colonic or rectal carcinoma and to compare these levels with the values of a control group of 130 healthy individuals. We have found that the frequency of average values of analyzed micronutrients in precancerous groups was decreasing in the order vit C > vit E/vit A > Se > beta-car. The average levels of vitamins and beta-carotene were significantly reduced in all carcinoma groups, while selenium level showed a decrease only in the gastric carcinoma group. Copper level was elevated in the ulcerative colitis group and in all groups with carcinoma. The results indicate a frequent insufficient saturation of organism by natural antioxidants in groups with precancerous lesions and carcinomas of stomach and colorectum. Therefore, it is necessary to increase the general consumption of fruits and vegetables in Slovakia as a part of primary prevention of malignant diseases in these organs. Chemoprevention may be recommended in individuals with precancerous lesions.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Case-Control Studies; Colorectal Neoplasms; Copper; Diet; Female; Humans; Male; Middle Aged; Precancerous Conditions; Selenium; Slovakia; Stomach Neoplasms; Vitamin A; Vitamin E; Zinc

Antioxidant vitamins have attracted considerable attention in previous studies of esophageal squamous-cell carcinoma, but dietary studies of adenocarcinoma of the esophagus and gastric cardia remain sparse. Treating these tumors as distinct diseases, we studied intakes of vitamin C, beta-carotene and alpha-tocopherol in a nationwide population-based case-control study in Sweden, with 185, 165, and 258 cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma, and gastric cardia adenocarcinoma, respectively, and 815 controls. Subjects with a high parallel intake of vitamin C, beta-carotene, and alpha-tocopherol showed a 40-50% decreased risk of both histological types of esophageal cancer compared with subjects with a low parallel intake. Antioxidant intake was not associated with the risk of gastric cardia adenocarcinoma. Separately, vitamin C and beta-carotene reduced the risk of esophageal cancers more than alpha-tocopherol. We found that antioxidant intake is associated with similar risk reductions for both main histological types of esophageal cancer. Our findings indicate that antioxidants do not explain the diverging incidence rates of the 2 histological types of esophageal cancer. Moreover, our data suggest that inverse associations with esophageal squamous-cell carcinoma and adenocarcinoma may be stronger among subjects under presumed higher oxidative stress due to smoking or gastroesophageal reflux, respectively. Our results may be relevant for the implementation of focused, cost-effective preventive measures.

Topics: Adenocarcinoma; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Squamous Cell; Cardia; Case-Control Studies; Diet; Dietary Supplements; Drug Synergism; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Humans; Male; Multivariate Analysis; Oxidative Stress; Risk Factors; Smoking; Stomach Neoplasms; Sweden; Vitamin E

Gastric cancer is generally thought to arise through a series of gastric mucosal changes, but the determinants of the precancerous lesions are not well understood. To identify such determinants, we launched a follow-up study in 1989-1990 among 3433 adults in Linqu County, China, a region with very high rates of gastric cancer.. Data on cigarette smoking, alcohol consumption, and other characteristics of the participants were obtained by interview in 1989-1990, when an initial endoscopy was taken. At study entry, antibodies to Helicobacter pylori were assayed in 2646 adults (77% of people screened), and levels of serum micronutrients were measured in approximately 450 adults. Follow-up endoscopic and histopathologic examinations were conducted in 1994. Antibodies to H. pylori, levels of serum micronutrients, and other baseline characteristics were compared between subjects whose condition showed progression to dysplasia or gastric cancer from study entry to 1994 and subjects with no change or with regression of their lesions over the same time frame. All P: values are two-sided.. The presence of H. pylori at baseline was associated with an increased risk of progression to dysplasia or gastric cancer (odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.2-2.6). The risk of progression to dysplasia or gastric cancer also was moderately increased with the number of years of cigarette smoking. In contrast, the risk of progression was decreased by 80% (OR = 0.2; 95% CI = 0.1-0.7) among subjects with baseline ascorbic acid levels in the highest tertile compared with those in the lowest tertile, and there was a slightly elevated risk in those individuals with higher levels of alpha-tocopherol.. H. pylori infection, cigarette smoking, and low levels of dietary vitamin C may contribute to the progression of precancerous lesions to gastric cancer in this high-risk population.

Topics: Adult; Ascorbic Acid; China; Disease Progression; Female; Follow-Up Studies; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Odds Ratio; Precancerous Conditions; Risk; Risk Factors; Smoking; Stomach; Stomach Neoplasms

Topics: Animals; Anti-Bacterial Agents; Ascorbic Acid; beta Carotene; Disease Progression; Drug Therapy, Combination; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Precancerous Conditions; Randomized Controlled Trials as Topic; Risk; Stomach Neoplasms; Treatment Outcome

Serum antioxidative vitamin levels and lipid peroxidation in gastric cancer patients were compared with values for age-matched healthy subjects. Blood samples were collected from the stomach of cancer patients scheduled for surgical removal of their tumor. Serum ascorbic acid, alpha-tocopherol, beta-carotene, and retinol in serum were determined by high-performance liquid chromatography, and malondialdehyde levels were analyzed spectrophotometrically. General health characteristics and taste preference for spicy and/or salty food were assessed by a self-administered questionnaire. Significant decreases in serum ascorbic acid and beta carotene were observed in stomach cancer patient as compared to the control group. The levels of ascorbic acid in patients with gastric carcinoma were less than one-fifth of the control. Beta carotene and alpha-tocopherol levels in the serum of the cancer patients were significantly decreased compared to the control group, but there were no differences in retinol between the groups. Serum malondialdehyde levels were significantly higher in the cancer patients than in controls. The levels of ascorbic acid and alpha-tocopherol tend to be lower in the patient with a preference for spicy and salty food than in others without the preference. Our results demonstrate that a correlation existed between the levels of serum ascorbic acid and beta carotene, alpha-tocopherol and lipid peroxidation in gastric carcinoma.

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Case-Control Studies; Chromatography, High Pressure Liquid; Feeding Behavior; Female; Humans; Lipid Peroxidation; Male; Malondialdehyde; Stomach Neoplasms; Surveys and Questionnaires; Vitamin A; Vitamin E; Vitamins

To examine the geographic associations between plasma antioxidant levels and gastric cancer risk, we conducted an ecological study in five regions of Japan representing the threefold variation in the disease mortality within the country. Subjects were 634 men aged 40-49 years sampled randomly from the five regions with 72% response rates. Plasma concentrations of five carotenoids (beta-carotene, alpha-carotene, lycopene, lutein, and zeaxanthin), alpha-tocopherol, and ascorbic acid were measured, and the mean levels were correlated with age-adjusted mortality rates from gastric cancer. beta-Carotene and alpha-tocopherol were inversely correlated with gastric cancer rates (r = -0.31 and -0.89, respectively). alpha-Carotene and lycopene showed stronger inverse correlation than did beta-carotene (r = -0.67 and -0.56, respectively), but these relations disappeared after the exclusion of one outlying region in Okinawa with the lowest mortality. In contrast, ascorbic acid revealed a negative correlation with the exclusion of this outlier (r = -0.61). Lutein and zeaxanthin were not inversely associated with risk. The results suggest that plasma levels of beta-carotene and alpha-tocopherol, and possibly alpha-carotene, lycopene, and ascorbic acid, may partly account for the regional difference in gastric cancer mortality in Japan.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Humans; Japan; Lutein; Lycopene; Male; Middle Aged; Stomach Neoplasms; Vitamin E; Xanthophylls; Zeaxanthins

Maori and Pacific Island ethnic groups in New Zealand have a high risk for gastric cancer. Low levels of gastric juice ascorbic acid (vitamin C) have been suggested to be a risk factor for gastric cancer. Previous studies have shown that gastric juice ascorbic acid may be independently associated with both ethnicity and Helicobacter pylori infection. This study aimed to examine the interrelationship between H. pylori and ethnicity in New Zealand.. Gastric juice was collected into 70% perchloric acid preservative and stored at -80 degrees C. Ascorbic acid was analysed by high-performance liquid chromatography using ion-pair chromatography and electrochemical detection. Inflammation and atrophy was graded from biopsies from multiple sites in the antrum and body. Gastric juice was collected from 89 patients during routine endoscopy.. There was a wide range of measured gastric juice ascorbic acid from 0.001 to 410 microg/mL. The median concentration of ascorbic acid for H. pylori-negative patients was 1.78 microg/mL (n = 57) and 0.12 microg/mL (n = 32) for H. pylori-positive patients (P = 0.001). Gastric juice ascorbic acid concentration was not associated with age, endoscopic diagnosis or intestinal metaplasia, but was significantly associated with the degree of acute inflammation (P = 0.01) and the presence of atrophy (P = 0.04). The median ascorbic acid concentration for European patients was 0.92 microg/mL (n = 44) and 0.09 microg/mL (n = 38) for Maori and Pacific Island ethnic groups combined (P = 0.1). Multiple step-wise regression analysis showed that only H. pylori infection was a significant factor for predicting ascorbic acid concentrations (r2 = 0.12).. This study has confirmed that gastric juice ascorbic acid concentration is lower in the presence of H. pylori infection.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Ascorbic Acid Deficiency; Biopsy; Cross-Cultural Comparison; Female; Gastric Juice; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Native Hawaiian or Other Pacific Islander; New Zealand; Risk Factors; Stomach Neoplasms

Gastric carcinogenesis is a multifactorial, multistep process, in which chronic inflammation plays a major role.. In order to ascertain whether free radical mediated oxidative DNA damage is involved in such a process, concentrations of 8-hydroxydeoxyguanosine (8OHdG), a mutagenic/carcinogenic adduct, and thiobarbituric acid reactive substances (TBARS), as an indirect measure of free radical mediated damage, were determined in biopsy specimens from patients undergoing endoscopy.. Eighty eight patients were divided into histological subgroups as follows: 27 with chronic non-atrophic gastritis, 41 with atrophic gastritis, six with gastric cancer, and 14 unaffected controls.. Intestinal metaplasia, Helicobacter pylori infection, and disease activity were semiquantitatively scored. 8OHdG concentrations were assessed by HPLC with electrochemical detection, and TBARS concentrations were fluorimetrically assayed.. 8OHdG concentrations (mean number of adducts/10(5) dG residues) were significantly higher in chronic atrophic gastritis (p = 0.0009). Significantly higher concentrations were also detected in the presence of severe disease activity (p = 0.02), intestinal metaplasia (p = 0.035), and H pylori infection (p = 0.001). TBARS concentrations were also higher in atrophic gastritis, though not significantly so. In a multiple logistic regression analysis, 8OHdG concentrations correlated best with the presence and severity of H pylori infection (r = 0.53, p = 0.002).. Chronic gastritis is characterised by the accumulation of oxidative DNA damage with mutagenic and carcinogenic potential. H pylori infection is the major determinant for DNA adduct formation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Analysis of Variance; Ascorbic Acid; Chronic Disease; Deoxyguanosine; DNA Damage; Female; Gastric Juice; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Reactive Oxygen Species; Regression Analysis; Stomach Neoplasms; Thiobarbituric Acid Reactive Substances

Vitamin C may be protective against gastric cancer though infection with Helicobacter pylori is associated with a reduction in intragastric concentrations of vitamin C.. To examine the effects of H pylori infection, gastric juice pH, the severity and extent of gastric inflammation, and CagA antibody status of the individual on gastric juice and mucosal vitamin C concentrations.. One hundred and fifteen patients undergoing routine gastroscopy for investigation of dyspepsia.. High performance liquid chromatography was used to determine vitamin C concentrations. CagA antibody was detected by western blot analysis.. Gastric juice ascorbic acid concentration was significantly lower in patients infected with H pylori compared with those uninfected (19.3 mumol/l (interquartile range (IQR) 10.7-44.5) versus 66.9 mumol/l (IQR 24.4-94.2), p = 0.003). The reduction in gastric juice ascorbic acid concentration was inversely related to the severity of gastritis (p = 0.01). CagA positive patients had significantly lower gastric juice ascorbic acid concentrations than CagA negative ones (14.8 mumol/1 (IQR 7.9-52.2) versus 39 mumol/l (IQR 19.9-142.2), p = 0.05). Decreased gastric juice dehydroascorbic acid concentrations were observed in patients with gastric atrophy and intestinal metaplasia. Mucosal ascorbic acid concentrations were also significantly lower in infected patients than uninfected patients (p = 0.04).. The reduction in gastric vitamin C concentrations is related to gastric juice pH, the severity and extent of gastritis, the presence of H pylori, and the CagA antibody status of the individual. These findings may have implications in H pylori associated carcinogenesis.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Antigens, Bacterial; Ascorbic Acid; Bacterial Proteins; Blotting, Western; Chromatography, High Pressure Liquid; Female; Gastric Juice; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Statistics, Nonparametric; Stomach Neoplasms

To explore the causes of the threefold variation in mortality rate from gastric cancer in Japan, we studied the geographic correlations between nutrient consumption and the disease in five Public Health Center districts including the regions with the highest and lowest mortality rates in the country. In the winters of 1989-1991, a three-day weighed food record was collected from 207 men and the wives of 165 of the men sampled from the five districts. The average daily consumption of selected nutrients was computed and correlated with the age-adjusted mortality rates from gastric cancer. Partial rank correlation coefficients adjusted for sex and other nutrients were 0.45, -0.80, -0.20, and -0.07 for sodium, carotene, ascorbic acid, and retinol, respectively. The results suggest that variation in gastric cancer mortality in Japan may be partly accounted for by the regional differences in consumption of sodium, carotene, and possibly ascorbic acid.

Topics: Adult; Alcohol Drinking; Ascorbic Acid; Carotenoids; Diet; Exercise; Female; Humans; Japan; Male; Middle Aged; Minerals; Nutritional Physiological Phenomena; Smoking; Sodium; Stomach Neoplasms; Vitamin A; Vitamins

Topics: Aged; Ascorbic Acid; Cohort Studies; Diet; Female; Humans; Male; Middle Aged; Netherlands; Nitrates; Risk Factors; Stomach Neoplasms

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Humans; Male; Middle Aged; Stomach Neoplasms

Helicobacter pylori infection is a risk factor for gastric carcinogenesis. High dietary vitamin C intake appears to protect against gastric carcinoma. It has been suggested that vitamin C exerts the protective effect by scavenging free radicals that may be enhanced by H. pylori. However, vitamin C has not been investigated in relation to the direct action on H. pylori. In this study, the authors attempted to clarify this possibility both in vitro and in vivo.. Susceptibility testing of H. pylori (64 strains) was performed by the agar dilution method. Bactericidal actions were determined by a broth cultivation technique. The effect of vitamin C on in vivo H. pylori colonization was evaluated by using the Mongolian gerbil model.. At concentrations of 2048, 512, and 128 microg/mL (minimum inhibitory concentrations [MICs]), vitamin C could inhibit the growth of 90% of the bacterial stains incubated at pH values of 7.4, 6.0, and 5.5, respectively. The broth cultures exposed to the MICs of vitamin C displayed a 1.57 approximately 2.5-log decrease in the number of viable bacteria, and the loss of viability was observed in 24 hours at concentrations 8-fold higher than the MICs. In an in vivo experiment, H. pylori colonies decreased significantly in animals treated with vitamin C after oral administration of vitamin C (10 mg/head/day) for 7 days.. High doses of vitamin C inhibit the growth of H. pylori in vitro as well as in vivo.

Topics: Animals; Ascorbic Acid; Gastric Mucosa; Gerbillinae; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Microbial Sensitivity Tests; Risk Factors; Stomach Neoplasms

The present study has examined the role of life-style on plasma and erythrocyte membrane lipid profile in 25 adult male gastric cancer patients as well as age and sex-matched controls. Total, free and LDH cholesterol were markedly elevated in plasma and erythrocyte membrane whereas HDL cholesterol and triglycerides were significantly reduced in gastric cancer patients. These changes can be attributed to alcohol consumption and cigarette smoking-risk factors in gastric carcinogenesis, associated with low levels of ascorbic acid and vitamin E.

Topics: Adenocarcinoma; Ascorbic Acid; Cholesterol; Cholesterol, LDL; Erythrocyte Membrane; Humans; Life Style; Lipids; Male; Middle Aged; Phospholipids; Stomach Neoplasms; Triglycerides; Vitamin E

Our objective was to identify the determinants of plasma levels of anti-oxidant vitamins which have been linked with decreased risk of cancer and other chronic diseases. Correlation analyses were performed between baseline plasma levels of ascorbic acid, alpha- and beta-carotenes, cryptoxanthin, lycopene and alpha- and gamma-tocopherols and baseline information on dietary and other demographic and life-style factors among 1,364 subjects 35-69 years of age, who are participants in a chemoprevention trial on pre-cancerous lesions of the stomach in Venezuela. Males had lower levels of ascorbic acid, alpha- and beta-carotene and cryptoxanthin and higher levels of alpha-tocopherol than females. This finding was confirmed in non-smokers and non-drinkers. In females, but not in males, age was positively associated with levels of ascorbic acid, cryptoxanthin, alpha- and beta-carotene and gamma-tocopherol. Male tobacco users had lower plasma levels of ascorbic acid, alpha- and beta-carotene and cryptoxanthin than nonusers, and regular alcohol drinkers had a decreased plasma levels of beta-carotene compared with non-drinkers. Female tobacco users had lower levels of ascorbic acid and cryptoxanthin than non-users, and regular alcohol drinkers had lower levels of ascorbic acid and lycopene than non-drinkers. Frequencies of consumption of fresh fruits, fruit juice, raw vegetables and plantains showed weak positive associations with plasma levels of several vitamins studied in both sexes. Sex, age in females, tobacco and alcohol use and dietary consumption affected plasma anti-oxidant vitamin levels in this population significantly. These factors may influence the effect of anti-oxidant treatment in intervention trials.

Topics: Adult; Age Factors; Aged; Antioxidants; Ascorbic Acid; Carotenoids; Double-Blind Method; Female; Humans; Male; Middle Aged; Risk Factors; Sex Factors; Stomach Neoplasms; Vitamin E; Vitamins

High dietary ascorbic acid intake appears to protect against gastric cancer. This may be due to its action as a scavenger of reactive radical species formed in the gastric mucosa, resulting in a reduced level of radical-mediated DNA damage. We have studied 82 patients, of whom 37 had Helicobacter pylori-associated gastritis, a condition which predisposes to gastric cancer. Using electron paramagnetic resonance (EPR) spectroscopy we have demonstrated, for the first time, that ascorbyl radicals are generated in human gastric mucosa, presumably as a result of scavenging of free radicals by ascorbic acid. Quantification of ascorbyl radicals demonstrates that there is a higher concentration in those patients with H.pylori gastritis compared with subjects with normal histology (P < 0.01). We also found gastric mucosal luminol-enhanced chemiluminescence and malondialdehyde concentrations (which are believed to be markers of radical generation and tissue damage) to be higher in patients with H.pylori gastritis compared with those with normal histology (P < 0.001 and P < 0.01 respectively). The observed concentrations of the ascorbyl radical correlate with the level of luminol-enhanced chemiluminescence (r = 0.41, P < 0.001), but not with malondialdehyde concentrations (r = 0.08, P = 0.47). Mucosal ascorbic acid and total vitamin C concentrations did not vary between histological groups, nor did they correlate with mucosal levels of the ascorbyl radical, chemiluminescence or malondialdehyde. These data suggest that ascorbic acid is acting as a scavenger of free radicals generated in human gastric mucosa. The experiments therefore provide direct supportive evidence for the hypothesis that ascorbic acid protects against gastric cancer by scavenging reactive radical species which would otherwise react with DNA, with resultant genetic damage.

Topics: Adult; Ascorbic Acid; Free Radical Scavengers; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Luminescent Measurements; Malondialdehyde; Middle Aged; Reactive Oxygen Species; Stomach Neoplasms

Serum micronutrient levels and their relationship to precancerous gastric lesions were studied in 600 subjects aged 35-64 years living in high-risk area of gastric cancer in Linqu County, Shandong Province. Serum micronutrient levels in local residents were 0.54 micrograms/ml, 0.29 micrograms/ml, 3.14 micrograms/ml, 9.62 micrograms/ml, 30.2 micrograms/L, 924 micrograms/L, 1 016 micrograms/L, and 42.0 micrograms/L for vitamin A, beta-carotene, vitamin C, vitamin E, selenium, zinc, copper and ferritin, respectively. Serum levels of beta-carotene, vitamin C and ferritin, and ratio of serum levels of zinc and copper correlated inversely to severity of pathological changes in gastric mucous membrane. With increase of serum level of beta-carotene or vitamin C, odds ratios (OR) of intestinal dysplasia and metaplasia lowered to 0.8, 0.6 and 0.9, 0.5, respectively, and with increase of those of both beta-carotene and vitamin C, their OR lowered further to 0.16, with patients of chronically atrophic gastritis as controls. It indicated maybe beta-carotene and vitamin C played a strong contributing role in protecting from development of precancerous gastric lesions.

Topics: Adult; Ascorbic Acid; beta Carotene; Carotenoids; Female; Gastric Mucosa; Humans; Male; Middle Aged; Precancerous Conditions; Stomach Neoplasms

CBA female mice treated with 1,2-dimethylhydrazine (DMH) alone or in combination with oestradiol dipropionate (EP) or ascorbic acid (AA) developed, as expected, a high incidence of uterine sarcomas. In addition, sarcomatous lesions at unusual sites (mainly in the forestomach) were evident. The incidence of sarcomatous lesions at other sites was 53/220 in mice having uterine sarcomas and 0/186 in mice treated with DMH but without uterine sarcomas. The difference between the two groups was highly statistically significant (P < 0.001) and demonstrates non-coincidental association of the above sarcomatous lesions with uterine sarcomas. Uterine sarcomas which presented in association with lesions at other sites were of a larger size than those found in isolation, and the difference in weights in three out of four groups was statistically significant (P = 0.008, 0.035 and 0.011). Histologically, sarcomatous lesions were similar in structure to those of uterine sarcomas, i.e. were of a fibroblastic-histiocytic nature with admixture of giant cells. On the basis of the above data the sarcomatous lesions described appear to represent uterine sarcoma metastases rather than independent primary tumours. AA did not have any influence on carcinogenesis induced by DMH alone but inhibited the growth of uterine sarcomas (whether or not they were associated with other sarcomatous lesions) induced by DMH combined with oestradiol dipropionate.

Topics: 1,2-Dimethylhydrazine; Animals; Ascorbic Acid; Carcinogens; Colonic Neoplasms; Dimethylhydrazines; Estradiol; Female; Incidence; Mice; Mice, Inbred CBA; Mutagens; Sarcoma; Stomach Neoplasms; Uterine Neoplasms

Topics: Adult; Ascorbic Acid; Cell Division; Child; Epithelium; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Male; Precancerous Conditions; Risk Factors; Stomach Neoplasms

H. pylori has recently been recognized as a novel risk factor of gastric cancer, but its precise role in gastric carcinogenesis is as yet unknown. The aim of the present study was to assess the relationship between H. pylori infection and vitamin C levels in gastric juice and also to examine whether eradication of H. pylori could have any impact on these levels. Gastric juice and plasma vitamin C levels were measured in 88 dyspeptic patients who had an upper gastrointestinal endoscopy. In the subgroup of H. pylori-positive patients, eradication was attempted with triple therapy. This subgroup was studied on two occasions, ie, before and after treatment. There were 58 H. pylori-positive and 30 -negative patients. Gastric juice vitamin C levels in H. pylori-positive patients were statistically lower (P < 0.001) than the levels in the H. pylori-negative patients. Triple therapy achieved eradication in 45 patients (77.6%) of the 58 H. pylori-positive patients. Before H. pylori was eradicated in these 45 patients gastric juice vitamin C levels were significantly (P < 0.001) lower than those after eradication, the latter being no different than the group of 30 H. pylori-negative patients. There was a significant (P < 0.001) improvement of gastritis after eradication, which paralleled the elevation of gastric juice vitamin C levels. No difference was noted in plasma vitamin C levels between H. pylori-negative and -positive patients or in the latter before and after H. pylori treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Ascorbic Acid; Bismuth; Drug Therapy, Combination; Female; Gastric Juice; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metronidazole; Organometallic Compounds; Stomach Neoplasms

Gastric juice ascorbic acid concentrations were examined in black and white patients. Significantly lower concentrations were found in blacks, in the absence of a significant difference in the plasma concentration of vitamin C between races. Blacks had higher prevalence of Helicobacter pylori infection, higher gastric pH, more severe acute and chronic inflammation of the gastric mucosa and higher frequency of Lewis (a-b-) phenotype. Although most of these factors have been related to low ascorbic acid levels in gastric juice, none of them could account entirely for the difference between races either individually or after joint consideration. These observations may help to explain the high incidence of gastric carcinoma among the black population in southern Louisiana.

Topics: Ascorbic Acid; Black People; Gastric Juice; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Louisiana; Stomach Neoplasms; White People

Topics: Adult; Ascorbic Acid; China; Esophageal Neoplasms; Humans; Middle Aged; Randomized Controlled Trials as Topic; Stomach Neoplasms

In experiment I, short-term effects of combined treatment with anti-oxidants, sodium ascorbate (NaAsA) and sodium nitrite (NaNO2) on forestomach cell proliferation were examined in F344 male rats. Groups of 5 animals aged 6 weeks were treated for 4 weeks with 0.8% catechol, 0.8% hydroquinone, 1% tert-butyl-hydroquinone (TBHQ), 2% gallic acid or 2% pyrogallor alone or in combination with 0.3% NaNO2 in the drinking water and/or 1% NaAsA in the diet. The thicknesses of forestomach mucosa in rats treated with anti-oxidants and NaNO2 in combination were greater than those with antioxidant alone and additional NaAsA treatment further enhanced the thickening of mucosa. It was noteworthy that values for mucosae of animals treated with NaNO2 and NaAsA without anti-oxidant were similar to those for anti-oxidants. In experiment 2, effects of combined treatment with NaAsA or ascorbic acid (AsA) and NaNO2 on carcinogenesis were examined in F344 male rats with or without N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) pre-treatment. Groups of 20 or 15 rats, respectively, aged 6 weeks, were given a single intra-gastric administration of 150 mg/kg body weight of MNNG in DMSO:water = 1:1 or the vehicle alone by stomach tube. Starting 1 week later, they received supplements of 1% NaAsA or 1% AsA in the diet and 0.3% NaNO2 in drinking water in combination, each of the individual chemicals alone, or basal diet until the end of week 52. In MNNG-treated animals, incidences of forestomach papillomas and carcinomas were significantly enhanced in the NaNO2 alone group (84 and 47%, respectively) as compared with the basal diet group (30 and 10%), with further significant increase in carcinomas occurring with additional NaAsA (79%, p < 0.05) or AsA (85%, p < 0.05) treatment. In animals without MNNG, all animals in the NaNO2 group demonstrated mild hyperplasia, additional administration of NaAsA or AsA remarkably enhancing the grade of hyperplasia, and resulting in 53% and 20% incidences, respectively, of papillomas. Thus NaNO2 was demonstrated to exert promoter action for forestomach carcinogenesis, with NaAsA and AsA acting as co-promoters. The results strongly indicate that combined treatment with NaAsA or AsA and NaNO2 may induce forestomach carcinomas in the long term.

Topics: Animals; Ascorbic Acid; Body Weight; Carcinoma, Squamous Cell; Drug Interactions; Kidney; Liver; Male; Methylnitronitrosoguanidine; Organ Size; Papilloma; Rats; Rats, Inbred F344; Sodium Nitrite; Stomach Neoplasms

Serum levels of retinol, beta-carotene, ascorbic acid, alpha-tocopherol, selenium, ferritin, copper, and zinc were assayed for approximately 600 adults aged 35 to 64 with pre-cancerous gastric lesions in an area of China with one of the world's highest rates of stomach cancer. Previous studies have shown that the cancers generally are preceded by chronic atropic gastritis (CAG), intestinal metaplasia (IM) and dysplasia. Concentrations of beta-carotene and ascorbic acid were significantly lower among individuals with IM than among those whose most severe lesion was superficial gastritis or CAG. The associations with IM for these nutrients were strong and independent. In combination, the odds of CAG progressing to IM were only 1/6 as high among those with upper tertile levels of beta-carotene and ascorbic acid as among those with lower tertile levels of both nutrients. The serum levels of beta-carotene and ascorbic acid were similar for individuals having IM with or without accompanying dysplasia. Risk of IM was also somewhat increased among those with low serum ferritin, but no significant effects were observed in multivariate analyses for the other nutrients assayed. The findings point to a major influence of specific nutrient deficits in the mechanisms of gastric carcinogenesis in this high-risk area.

Topics: Adult; Ascorbic Acid; beta Carotene; Carotenoids; China; Copper; Female; Ferritins; Humans; Male; Middle Aged; Minerals; Multivariate Analysis; Precancerous Conditions; Selenium; Smoking; Stomach Neoplasms; Vitamin A; Vitamin E; Vitamins; Zinc

A case-control study of dietary factors and gastric cancer was conducted between September 1986 and March 1989 in the Barcelona metropolitan area, Spain. In all 117 cases with histologically confirmed diagnosis of gastric adenocarcinoma were matched on sex, age and possession of a telephone to 234 population controls. Of the controls 188 (80.3%) were selected by random digit telephone dialing and 46 (19.7%) by neighbourhood of residence. Information about frequency and amount of consumption of 89 alimentary items was gathered by questionnaire, and cases and controls were interviewed in their homes by trained interviewers. The gastric cancer risk decreased in proportion to vitamin C intake. In multivariate analysis adjusting for major covariables, energy and vitamin A intake, the estimated odds ratio (OR) for the upper quartile of vitamin C intake was 0.3 (95% confidence interval [CI]: 0.1-0.8). After adjustment for major covariables, calories and vitamin C intake, vitamin A did not show significant association with the gastric cancer risk. Our findings are consistent with previous case-control studies and with the hypothesis that vitamin C may inhibit the intragastric nitrosation process.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Case-Control Studies; Diet; Energy Intake; Female; Humans; Interviews as Topic; Male; Middle Aged; Odds Ratio; Risk Factors; Smoking; Spain; Stomach Neoplasms; Surveys and Questionnaires; Vitamin A

The effects of four fruit juices, processed vegetable juice, orange peel, green tea and low dose vitamin C on endogenous N-nitrosation in 86 subjects from a high-risk area for gastric cancer in Moping County, China were studied using urinary excretion of N-nitrosoproline (NPRO) as an indicator. After ingestion of 300 mg L-proline, urinary excretion of NPRO was significantly increased from a baseline of 2.5 +/- 1.6 micrograms/day to 8.7 +/- 6.2 micrograms/day. (P < 0.001). Vitamin C (75 mg) administration significantly reduced NPRO formation (62.3%, P < 0.002) although NPRO excretion remained higher than the baseline level (4.2 +/- 1.3 vs 2.2 +/- 1.2 micrograms/day, P < 0.001). Intake of fruit juices and green tea extracts (containing 75 mg vitamin C) or of orange peel powder (containing 3 mg vitamin C) together with 300 mg L-proline inhibited NPRO formation effectively to the baseline level or to levels significantly lower than the baseline level (P < 0.05-0.005). A processed juice of a number of vegetables (300 ml) significantly catalysed endogenous nitrosation (14.7 +/- 11.8 vs 9.4 +/- 4.7 micrograms/day, P < 0.05). Endogenous N-nitrosation was unaffected by the presence of intragastric lesions. The present study shows that endogenous nitrosation in this population is profoundly affected by environmental factors and that inhibitors, such as vitamin C, alpha-tocopherol and other non-nutritive compounds in the foods do inhibit endogenous nitrosation either synergistically or in an additive manner. The significance of fruits and vegetables in prevention of human cancers is discussed.

Topics: Ascorbic Acid; Beverages; China; Citrus; Female; Fruit; Gastric Mucosa; Gastritis; Humans; Male; Metaplasia; Middle Aged; Nitrosamines; Precancerous Conditions; Proline; Risk Factors; Stomach Neoplasms; Tea; Vegetables

The effects of the synthetic antioxidant butylated hydroxyanisole (BHA) and naturally occurring antioxidants such as L-ascorbic acid (AsA; vitamin C), citric acid, benzoic acid or gallic acid in combination, on the development of rat forestomach epithelial lesions were investigated. A dietary level of 2.0% was selected for all antioxidants and the experimental period was 1 year. As compared with BHA alone, treatment with AsA in combination with BHA increased the severity of the hyperplasia in the mid-region, but not in the prefundic region of the forestomach epithelium, as well as the multiplicity of forestomach tumors. Furthermore, incidences of squamous cell carcinomas (SCCs) in the forestomach were significantly elevated in this group, while papilloma development only showed a tendency to increase. In addition, SCC invasion into the muscle layer of the forestomach was observed only in the BHA + AsA group. Treatment with the other antioxidants did not affect BHA-induced forestomach lesion development. The present study demonstrated that AsA can clearly enhance BHA forestomach carcinogenesis.

Topics: Animals; Ascorbic Acid; Butylated Hydroxyanisole; Cocarcinogenesis; Drug Synergism; Epithelium; Food Additives; Male; Rats; Rats, Inbred F344; Stomach; Stomach Neoplasms

Gastric juice ascorbic acid, total vitamin C, nitrite and N-nitroso-compound concentrations were determined in fasting gastric juice from four second generation members of a gastric cancer family, all of whom had Helicobacter pylori-associated chronic gastritis and intestinal metaplasia. Juice pH, nitrite and N-nitroso-compound concentrations were low. Juice ascorbate levels were comparable to those found in subjects with normal histology. The findings are contrary to our previous experience with juice ascorbate in H. pylori gastritis.

Topics: Adult; Ascorbic Acid; Family Health; Gastric Juice; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Hydrogen-Ion Concentration; Nitrites; Nitroso Compounds; Stomach Neoplasms

Ascorbic acid has been shown to decrease nitrosation in vivo, and epidemiological data suggest that the consumption of foods rich in this vitamin is associated with a reduced risk for gastric cancer. In order to study this suggestion further, fasting gastric juice samples were obtained from 62 high-risk patients (seven with atrophic gastritis, ten with pernicious anaemia, ten with partial gastrectomy, 21 with vagotomy and drainage and 14 with highly selective vagotomy), before, during four weeks' treatment with 1 g ascorbic acid four times daily, and four weeks after treatment. Samples were analysed for pH, total and nitrate-reducing bacterial counts, nitrite and N-nitroso compounds. Treatment with ascorbic acid lowered the median pH only in the vagotomized patients (p less than 0.001) but resulted in a reduction in median nitrate-reducing bacterial counts and in nitrite and N-nitroso compound concentrations in all groups, except for an increase in the nitrate-reducing bacterial count in atrophic gastritis patients and in nitrite in those with pernicious anaemia. These data suggest that treatment with a high dose of ascorbic acid reduces the intragastric formation of nitrite and N-nitroso compounds.

Topics: Adult; Aged; Ascorbic Acid; Female; Gastric Juice; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Nitrites; Nitroso Compounds; Risk; Stomach Neoplasms

Although gastric cancer is the most common cause of mortality from cancer, its etiology is not yet clear. To elucidate the role of N-nitroso compounds, we investigated 30 cases of gastric cancer by determination of the contents of nitrate and ascorbic acid and by detection of mutagens in urine. Cases were paired 1:1 with patients with dysplasia and normal controls of the same sex and age group. In comparison with normal controls, the gastric cancer group had higher nitrate and lower ascorbic acid levels in urine. Mutagenicity was observed in the urines of 83.3% of the gastric cancer cases and in 16.6% of the dysplasia group, but in none of those from normal controls. When the N-nitroso compound content of gastric juice was determined, the levels in control subjects were significantly lower than those in persons with gastric cancer. These results support the hypothesis that the cause of gastric cancer may be N-nitroso compounds.

Topics: Ascorbic Acid; Gastric Juice; Humans; Nitroso Compounds; Stomach Neoplasms

In animal experiments with Wistar rats we attempted to determine if oral application of Vitamin C inhibits or delays carcinogenesis due to oral administered N-Nitrosopiperidine (NTP). One group of animals received NTP only, two other groups NTP and Vitamin C either alternating or simultaneously. A fourth group receiving only Vitamin C served as control. Carcinomas of the esophagus, stomach and liver developed in response to NTP application. The additional administration of Vitamin C neither inhibited nor delayed the development of carcinomas.

Topics: Animals; Anticarcinogenic Agents; Ascorbic Acid; Carcinogens; Dose-Response Relationship, Drug; Esophageal Neoplasms; Female; Liver Neoplasms; Male; Neoplasms, Experimental; Nitrosamines; Rats; Rats, Inbred Strains; Stomach Neoplasms

In 1971-1973 at the third examination of the Basel Study started in 1959, the major antioxidant vitamins and carotene were measured in the plasma of 2974 men. A subsample and their families were reinvestigated in 1977-79. During the 12-y observation period (1973-85) 553 men died, 204 of cancer (lung cancer 68, stomach cancer 20; colon cancer 17, all other malignancies 99). We found significantly lower mean carotene levels for all cancer, bronchus cancer, and stomach cancer (all P less than 0.01) compared with the 2421 survivors. The relative risk of subjects with low carotene (less than 0.23 mumol/L) was significantly elevated (P less than 0.05) for lung cancer (Cox's model). Higher risks were noted for all cancer (P less than 0.01) if both carotene and retinol were low. Low plasma carotene which is known to reflect carotene intake is in our study associated with increased cancer risk.

Topics: Adult; Age Factors; Ascorbic Acid; beta Carotene; Carotenoids; Cholesterol; Cohort Studies; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Risk Factors; Sex Factors; Smoking; Stomach Neoplasms; Switzerland; Triglycerides; Vitamin A; Vitamin E

To determine the relevance of gastric juice factors to gastric carcinogenesis, 56 patients with unoperated stomachs undergoing endoscopy for dyspepsia had gastric juice aspirated and analysed for pH, ascorbic acid, total bile acids, nitrite, nitrate and total nitroso compounds (NOCs). Plasma was obtained for vitamin C estimation. Antral and body biopsies were assessed for gastritis, Helicobacter pylori, atrophy and intestinal metaplasia (IM). Patients with chronic atrophic gastritis (n = 17) had lower gastric juice ascorbic acid concentrations (P less than 0.001), higher pH (P less than 0.05) and higher incidence of H. pylori infection (P less than 0.001) than normal subjects (n = 12). Patients with reflux gastritis (n = 9) had higher total bile acids (P less than 0.01). Patients with chronic gastritis and IM (n = 11) had higher gastric juice pH (P less than 0.01) and total bile acid concentrations (P less than 0.05), and lower gastric ascorbic acid concentrations (P less than 0.01) than those with chronic gastritis and no IM (n = 24). In chronic gastritis, high nitrite concentrations were associated with high pH (P less than 0.01). However, there were no significant differences in plasma vitamin C or gastric nitrite, nitrate or total NOC concentrations in relation to gastric histology. We conclude that the premalignant condition IM is associated with H. pylori infection, low gastric ascorbic acid levels and elevated total bile acids, but not to elevation in nitrite or total NOCs in fasting gastric juice.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Atrophy; Bile Acids and Salts; Gastric Juice; Gastric Mucosa; Humans; Intestines; Metaplasia; Middle Aged; Nitrates; Nitrites; Nitroso Compounds; Precancerous Conditions; Stomach; Stomach Neoplasms

Plasma antioxidant vitamins A, C, and E and carotene were measured in a group of 2,974 men participating in the third examination of the prospective Basel Study in 1971-1973. In 1985, the vital status and mortality of all participants were assessed. A total of 204 men had died from cancer, including 68 with bronchus cancer and 37 with gastrointestinal cancer (20 with stomach cancer and 17 with large bowel cancer excluding cancer of the rectum). Overall mortality from cancer was associated with low mean plasma levels of carotene adjusted for cholesterol (p less than 0.01) and of vitamin C (p less than 0.01). Bronchus and stomach cancers were associated with a low mean plasma carotene level (p less than 0.01). Subjects with subsequent stomach cancer also had lower mean vitamin C and lipid-adjusted vitamin A levels than did survivors (p less than 0.05). After calculation of the relative risk using the Cox model with exclusion of mortality during the first 2 years of follow-up, low plasma carotene (below quartile 1) was associated with a significantly increased risk for bronchus cancer (relative risk (RR) = 1.8, p less than 0.05), low plasma levels of carotene and vitamin A with all cancers (RR = 2.47, p less than 0.01), and low plasma retinol in older subjects (greater than age 60 years) with lung cancer (RR = 2.17, p less than 0.05). Low levels of vitamin C increased the risk of stomach cancer (RR = 2.38) and gastrointestinal cancer (RR = 2.46) in older subjects, but only significantly with the inclusion of the first 2 years. The authors conclude that low plasma levels of antioxidant vitamins are associated with an increased risk of subsequent cancer mortality. This effect was stronger in men above age 60 years at blood sampling, and the effect seems to be site-specific.

Topics: Adult; Age Factors; Aged; Antioxidants; Ascorbic Acid; Bronchial Neoplasms; Carotenoids; Female; Follow-Up Studies; Gastrointestinal Neoplasms; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; Risk Factors; Stomach Neoplasms; Time Factors; Vitamin A; Vitamin E; Vitamins

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Bronchial Neoplasms; Carotenoids; Colonic Neoplasms; Humans; Lipids; Middle Aged; Neoplasms; Prospective Studies; Risk Factors; Stomach Neoplasms; Vitamin A; Vitamin E

The effects of tea extracts and their ingredients, catechins and L-ascorbic acid (AsA), on the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were examined in vitro and in the stomachs of rats using E. coli WP2 and S. typhimurium TA100. The extracts of green tea and black tea leaves decreased the mutagenic activity of MNNG to E. coli WP2 in vitro in a desmutagenic manner. Catechins such as (-)-epigallocatechin from green tea leaves and the low-molecular-weight tannin fraction isolated from black tea extract with HP-20 resin also exhibited inhibitory effects against the mutagenic activity of MNNG. A desmutagenic effect of AsA on MNNG-induced mutagenicity was observed depending on the dose, though it was complicated. The effects were also demonstrated in the stomachs of rats by assaying the bacterial mutagenic in vitro; the tea extracts previously given orally to rats reduced the mutagenic activity of MNNG remarkably, though simultaneous administration showed less effect. The effectiveness of tea extracts for the decrease of MNNG-induced mutagenesis in vitro and in vivo suggests that the habitual drinking of tea may reduce the tumor-initiating potency of MNNG-type nitrosoureido compounds if they are formed in the stomach.

Topics: Animals; Ascorbic Acid; Catechin; Escherichia coli; Methylnitronitrosoguanidine; Mutagenicity Tests; Mutation; Plant Extracts; Rats; Salmonella typhimurium; Stomach Neoplasms; Tea

Fasting gastric juice pH and concentrations of vitamin C in gastric aspirate and plasma were measured in 73 patients undergoing endoscopy. Vitamin C concentrations were significantly lower in those with hypochlorhydria (pH greater than 4; n = 23) compared with those with pH less than or equal to 4 (p less than 0.005) and there was a significant correlation between gastric juice and plasma concentrations (p = 0.002). Patients with normal endoscopic findings had significantly higher intragastric concentrations of vitamin C than those with gastric cancer (p less than 0.001), pernicious anaemia (p less than 0.005), gastric ulcer (p less than 0.01), duodenal ulcer (p less than 0.05), or after gastric surgery (p less than 0.01). There was a strong trend (0.05 less than p less than 0.1) towards lower intragastric concentrations of vitamin C in patients with chronic atrophic gastritis. In vitro, vitamin C concentrations remained stable in acidic but fell significantly over 24 hours in alkaline gastric aspirate. Gastric secretory studies in five volunteers showed that vitamin C concentrations increased significantly after intramuscular pentagastrin. These findings suggest that the low fasting levels of vitamin C in hypochlorhydric gastric juice may be caused by chemical instability and that vitamin C may be secreted by the human stomach.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Pernicious; Ascorbic Acid; Diet; Duodenal Ulcer; Female; Gastrectomy; Gastric Acidity Determination; Gastric Juice; Humans; Male; Middle Aged; Stomach Diseases; Stomach Neoplasms; Stomach Ulcer

Urine and blood levels of ascorbic acid (AA) were measured in healthy subjects (40), cases of cancer of the lung (74), stomach (32) and esophagus (12). AA levels were decreased in cancer patients, particularly, in those with gastric and esophageal tumors. A correlation between the decrease of AA level and the increase in blood concentrations of malonic and pyruvic acids was established. Administration of 1.5 g AA for 7 days was followed by blood-AA level returning practically to normal matched by decrease in lactate and pyruvate concentrations. Also, a correlation between postoperative complication frequency and AA deficit was shown. Correction of AA level was found to be an effective means of postoperative complication prevention.

Topics: Administration, Oral; Ascorbic Acid; Ascorbic Acid Deficiency; Combined Modality Therapy; Esophageal Neoplasms; Humans; Infusions, Intravenous; Lactates; Lactic Acid; Lung Neoplasms; Oxidation-Reduction; Preoperative Care; Pyruvates; Pyruvic Acid; Stomach Neoplasms

Epidemiological studies have implicated that betel quid offers some protection to tobacco induced carcinogenesis. Earlier studies in our laboratory have shown betel leaf extract (BLE) to be antimutagenic against standard mutagens and tobacco-specific N'-nitrosamines (TSNA), N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the present study, we have tested the anticarcinogenic effect of BLE using Swiss male mice. Two protocols of study were used to test this effect. In the first protocol, the effect of BLE was tested against the standard carcinogen benzo[a]pyrene (BP) using Wattenberg's stomach tumor model, Cancer Res., 41 (1981) 2820-2823. In this protocol, BLE inhibited the tumorigenicity of BP to a significant extent. In the second protocol, the effect of BLE against the two tobacco-specific nitrosamines, NNN and NNK was studied using long-term studies on Swiss male mice. The nitrosamines were administered on the tongues of the mice, while the BLE was supplied in drinking water. Two doses of NNN (22 mg and 72 mg) and one dose of NNK (22 mg) were used. In this study, it was observed that the number of tumor bearing animals decreased, but the difference was significant only in the group treated with the low dose of NNN in combination with BLE. However, in all the BLE treated animals, irrespective of the dose of nitrosamine, the hepatic vitamin A and C levels were elevated significantly as compared to the corresponding nitrosamine-treated controls. These results indicate that BLE has a promising anticarcinogenic role to play in tobacco induced cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Areca; Ascorbic Acid; Benzo(a)pyrene; Carcinogens; Drug Interactions; Liver; Male; Mice; Mice, Inbred Strains; Nicotiana; Nitrosamines; Plant Extracts; Plants, Medicinal; Plants, Toxic; Stomach Neoplasms; Tobacco, Smokeless; Vitamin A

We found that wheat bran acted as a nitrite scavenger under conditions similar to those that exist in the stomach. Wheat flour and cellulose did not act as nitrite scavengers. Wheat bran, at a concentration equivalent to that in the stomach after ingestion of about two pieces of whole-wheat bread, reduces the nitrite concentration from 20 microM to about 10 microM in 60 min at pH 3.5 and 37 degrees C. At pH 2.5 and 1.5, most of the nitrite had disappeared in 10 min. At pH less than or equal to 2.5 the nitrite scavenging effect of bran was as efficient as that of ascorbic acid. Ferulic acid, a component of bran, reacted rapidly with 20 microM-nitrite both at pH 3.5 and 1.5, whereas phenolic lignin model compounds only reacted at pH 1.5.

Topics: Ascorbic Acid; Coumaric Acids; Dietary Fiber; Humans; Hydrogen-Ion Concentration; Lignin; Nitrites; Polymers; Stomach Neoplasms; Triticum

A case-control study of gastric cancer was done in a rural area of northern Kyushu, Japan, in relation to dietary habits especially focusing on the relationship with the consumption of broiled fish. The study was based upon 139 cases of newly diagnosed gastric cancer at a single institution, 2,574 hospital controls and 278 controls sampled randomly from the residents of the study area (with sex and year of birth matched). No association was observed between the consumption of broiled fish and gastric cancer risk whether three types of broiled fish (raw fish, dried fish and salted fish) were analyzed separately or as a single category. However, consistently in the comparisons with both sets of controls, the risk of gastric cancer was inversely related with the consumption of fruits and positively associated with cigarette smoking. A decreased risk of gastric cancer was also noted among those with high consumption of green tea (10 or more cups per day).

Topics: Adult; Aged; Animals; Ascorbic Acid; Diet; Female; Fishes; Fruit; Humans; Japan; Male; Middle Aged; Risk Factors; Smoking; Stomach Neoplasms

It was shown in experiments on 186 mice that formation of tumors of the lung and fore-stomach induced by injection of sodium nitrite in combination with aminopyrine or methylurea is inhibited following treatment with ascorbic acid, hexamethylenetetramine or sodium metabisulfite.

Topics: Aminopyrine; Animals; Ascorbic Acid; Cocarcinogenesis; Female; Lung Neoplasms; Male; Methenamine; Methylurea Compounds; Mice; Mice, Inbred Strains; Nitrites; Sodium Nitrite; Stomach Neoplasms; Sulfites

A case-control investigation involving interviews with 564 stomach cancer patients and 1131 population-based controls was conducted to evaluate reasons for the exceptionally high rates of stomach cancer in Linqu, a rural county in Shandong Province in northeast China. Daily consumption of sour pancakes, a fermented indigenous staple, was associated with a 30% increase in risk. Risks of stomach cancer were also increased by 2- to 3-fold among persons with prior chronic gastritis or gastric ulcer, by 80% among those with stomach cancer in a family member, by 50% among men who smoked one or more packs of cigarettes/day, by 40% among those who preferred salty foods, and by 50% among families with moldy grain supplies. In contrast, risks tended to decrease in proportion to increasing consumption of fresh vegetables and fruits. This protective effect was more pronounced for vegetables, with those in the highest quartile of intake at less than one-half the risk of those in the lowest. Stomach cancer risks also declined with increasing dietary intake of carotene, vitamin C, and calcium, but not retinol. These findings provide leads to dietary factors that contribute to the high rates in Linqu, where stomach cancer is the leading cause of cancer and has not yet begun to decline as in other parts of the world.

Topics: Adult; Aged; Ascorbic Acid; Calcium, Dietary; China; Diet; Feeding Behavior; Female; Gastritis, Atrophic; Humans; Male; Middle Aged; Regression Analysis; Risk Factors; Smoking; Sodium Chloride; Stomach Neoplasms; Vegetables

Topics: Adult; Alcoholism; Ascorbic Acid; Esophageal Neoplasms; Female; Gastrointestinal Neoplasms; Humans; Intestinal Neoplasms; Male; Middle Aged; Nutritional Physiological Phenomena; Risk Factors; Stomach Neoplasms

In the last few years, a great deal of attention has been paid to the hypothetical relationship between high nitrate intake, N-nitroso-compounds and gastric cancer. This long term study deals with the effect of nitrate and ascorbic acid contained in drinking water on the development of cancer in operated stomachs of rats without additional application of a carcinogen (tumor model). A total of 147 F1-Hybrids of WELS/Fohm X BD IX--rats were subjected to stomach operation (Gastroenterostomia antecolica anterior, truncular vagotomy and pyloroplasty). Carcinomas in stomach occurred within 33 weeks (post operationem). The surgical procedures altered the gastric flora, resulting in an increase and predominance of nitrate-reducing bacteria. The maximal tumor rate (10 of 13 rats) occurred in rats with gastroenterostomy and additional nitrate exposition. It may be possible, the nitrate is a precursor of gastric carcinogenesis. But we could not give any significant evidence of this fact. The addition of ascorbic acid to the drinking water lead to a suppression of the development of tumors. Our experience with the tumor model "operated stomach" underline the multifactorial genesis of stomach cancer in rats.

Topics: Animals; Ascorbic Acid; Drinking; Female; Gastroenterostomy; Male; Nitrates; Postoperative Complications; Pylorus; Rats; Stomach; Stomach Neoplasms; Vagotomy; Water Supply

Topics: Aged; Ascorbic Acid; beta Carotene; Carotenoids; Colonic Neoplasms; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prospective Studies; Rectal Neoplasms; Smoking; Stomach Neoplasms; Switzerland; Vitamin A; Vitamin E

A survey was conducted of 513 men aged 65 74 years living in two British towns with high and low stomach cancer death-rates. The prevalence of severe atrophic gastritis (defined as a serum pepsinogen I less than 20 micrograms l-1) was significantly higher in the high-risk than in the low-risk town (14.5% and 7.7% respectively); it also tended to be higher in the manual workers, who are known to have a greater risk of stomach cancer than non-manual workers. The manual workers in the high-risk town were particularly likely to have had a partial gastrectomy. Plasma ascorbate concentration and fruit intake were lower in the high-risk area and lower social classes, suggesting a poorer vitamin C status. There was, however, no direct relationship between ascorbate concentration and the presence of severe atrophic gastritis. These findings are consistent with the hypothesis that risk of stomach cancer is determined in two stages--a long-term effect, producing atrophic gastritis; and a short-term effect in which vitamin C is protective.

Topics: Aged; Ascorbic Acid; Gastritis; Gastritis, Atrophic; Humans; Male; Risk; Stomach Neoplasms; United Kingdom

It has been hypothesized that dietary nitrate and nitrite are converted in the stomach to nitrous acid, which reacts with secondary amines and amides to form nitrosamines and nitrosamides, compounds frequently demonstrated to be carcinogenic in animals, and that vitamins C and E inhibit N-nitroso product formation by chemically reducing nitrous acid. This hypothesis and others were tested in a case-control study (controls were individually matched by age, sex and area of residence), utilizing a standardized, quantitative, dietary history questionnaire interview. Daily nutrient consumption values were calculated from interview responses, and continuous conditional logistic regression was used for the data analysis. Significant findings are as follows: (1) Average daily consumption of nitrite, chocolate and carbohydrate was associated with increasing trends in risk. (2) While citrus fruit intake appeared to be somewhat protective, any protective effect of vitamin C intake was less apparent, and of vitamin E, not at all apparent. (3) Consumption of dietary fibre was negatively associated with gastric cancer risk. These findings appear to implicate a number of dietary components, including nitrite consumption, in the genesis of gastric cancer in humans.

Topics: Adult; Aged; Ascorbic Acid; Biotransformation; Diet; Epidemiologic Methods; Feeding Behavior; Female; Fruit; Humans; Male; Middle Aged; Nitroso Compounds; Stomach Neoplasms; Vitamin E

Three samples of 24-h urine were collected from each of 104 inhabitants of high-risk (Akita) and low-risk (Iwate) areas for stomach cancer in northern Japan, according to the following protocols: (i) when they were undosed, (ii) after ingestion of proline three times a day and (iii) after ingestion of proline together with vitamin C three times a day. These samples were analysed for N-nitrosamino acids, nitrate and chloride ion as indices of the exposure. The median values of N-nitrosoproline (NPRO) and N-nitroso-2-methylthiazolidine 4-carboxylic acid (NMTCA) excreted in the urine of undosed subjects were not different between the two areas; however, that of N-nitrosothiazolidine 4-carboxylic acid (NTCA) was significantly higher in subjects of the high-risk area. Salt intake, estimated from the level of chloride ion in the urine, did not differ in two areas. After intake of proline, the NPRO level increased significantly only in subjects of the high-risk area, but not in those of the low-risk area; intake of vitamin C inhibited this increase of NPRO and lowered the levels of other nitrosamino acids only in the high-risk subjects. In contrast, the urinary level of nitrate was higher in subjects of the low-risk area than in those of the high-risk area; nitrate levels were found to correlate well with the amounts of vegetables consumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Ascorbic Acid; Chlorides; Feeding Behavior; Humans; Japan; Nitrates; Nitrosamines; Nitroso Compounds; Risk Factors; Smoking; Stomach Neoplasms; Thiazoles; Thiazolidines

Urinary excretion of N-nitrosoproline (NPRO) following ingestion of a high-nitrate salad meal, without then with an oral dose of 500 mg L-proline, was investigated in 16 healthy volunteers. The mean excretion rate following consumption of the high-nitrate meal alone was significantly lower than that measured after ingestion of the salad plus proline. Supplementation of the same meal (plus proline) with vitamin C from dietary sources resulted in a significant decrease in mean urinary NPRO levels in healthy subjects. The nitrosation-inhibiting effect of vitamin C was not affected by an increase in the fat content of the meal. Supplementation of the high-nitrate salad with alcohol or coffee did not affect subsequent urinary NPRO levels. No significant difference was observed in the urinary NPRO concentrations of smokers and nonsmokers after ingestion of high-nitrate salad (with or without vitamin C) plus proline.

Topics: Ascorbic Acid; Diet; Humans; Nitrates; Nitrites; Nitrosamines; Proline; Saliva; Stomach Neoplasms

A hospital-based case-control study of gastric cancer precursor lesions was conducted in a high-risk black population in southern Louisiana. Ninety-three subjects with biopsy-proved advanced chronic atrophic gastritis were compared to two control series: a gastroscopy clinic series and a general hospital-admission series. Dietary case-control differences indicated a protective effect associated with fruit and vegetable intake and with dietary vitamin C and a risk elevation associated with milk consumption. The protective effect associated with consumption of fruits, vegetables, and vitamin C is consistent with findings for gastric cancer and with the etiologic hypothesis of intragastric nitrosation. A twofold increased risk was associated with cigarette smoking. Gastric juice pH, NO3-, and NO2- were determined for subjects undergoing gastroscopy, and comparisons were made between this high-risk U.S. group and a Colombian population with a much greater magnitude of risk; the latter had higher NO3- and NO2- levels. An increase in pH was associated with increasing severity of gastric lesions. Levels of pH and NO2- concentration were significantly correlated (P less than .0005); however, in Louisiana the large difference in NO2- concentration associated with pH elevation is not associated with histopathologic severity. Divergent trends with severity of lesions for NO3- concentration were seen in the two populations.

Topics: Adult; Age Factors; Aged; Animals; Ascorbic Acid; Black People; Chronic Disease; Diet; Female; Fruit; Gastric Acidity Determination; Gastric Juice; Gastritis; Gastritis, Atrophic; Humans; Male; Middle Aged; Milk; Nitrates; Nitrites; Sex Factors; Smoking; Sodium Chloride; Stomach Neoplasms; Vegetables

Carcinogenic and promoting effects of RRME as isolated from the pickled vegetables in Linxian County, a high incidence area of esophageal cancer, were studied in mice and rats. RRME alone did not cause tumor in the forestomach of mice and esophagus of rats. When the mice were intubated with a single dose of nitroso-sarcosine-ethylester (NSEE), the incidence of the forestomach carcinoma was only 9.5%. However, when the mice were given gastric doses of RRME after one single dose of NSEE, the incidence was increased to 41.0%. In rats, the tumor incidence was 5.3% in nitroso-methylbenzylamine (NMBzA) group, while in NMBzA kRME group, it was 20.7%. In rats intubated with NSEE for 7 times, no carcinoma appeared in esophageal epithelium; while followed by gastric doses of RRME, the incidence of esophagus carcinoma increased up to 63.2%. The experimental results show that RRME has distinct promoting effect on the process of cocarcinogenesis initiated by NSEE and NMBzA in the forestomach of mice and esophagus of rats, but without carcinogenic effect itself. Retinamide (RI) and massive dose of vitamin C showed an obviously inhibitory effect on promoting action of RRME in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Dimethylnitrosamine; Esophageal Neoplasms; Female; Mice; Nitroso Compounds; Rats; Rats, Inbred Strains; Stomach Neoplasms; Tretinoin

The effect of vitamins A, C and E, butylated hydroxytoluene (BHT) and glutathione (GSH) on gastric carcinogenesis induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was investigated. Male and female BD-VI rats 2-3 months old received a single oral application of MNNG dissolved in corn oil. The male rats were divided into four groups: Group-I: MNNG 250 mg/kg by intubation; Group-II: MNNG + vitamin C daily in the drinking water (400 mg/l); Group-III: MNNG + vitamin C (400 mg/l) + 100 g of milk broth (for each of 10 rats) containing vitamin A (40,000 IU), vitamin E (0.5 g) and BHT (0.1 g) three times a week. The treatment with antioxidants started 7 days before the MNNG administration and continued until the end of experiment. Group-IV rats received MNNG + oxyferriscorbone, i.p. as a single dose of 1.0 mg/kg, daily during the week before and the week after MNNG exposure and than 3 times a week till the end of the experiment. Female rats were divided into two groups: Group-I: MNNG 333 mg/kg by intubation; Group-II: MNNG + GSH orally at a dose of 100 mg/rat 1 h before and 5, 24, 48, and 72 h after MNNG intubation. The incidence of gastric tumors after 15 months of treatment was as follows: male rats, 82.4% in Group-I, 40.0% in Group-II, 40.7% in Group-III, and 50.0% in Group-IV; female rats; 72.7% in Group-I, and 36.0% in Group-II.

Topics: Animals; Antioxidants; Ascorbic Acid; Butylated Hydroxytoluene; Drug Interactions; Female; Glutathione; Male; Methylnitronitrosoguanidine; Rats; Stomach Neoplasms; Vitamin A; Vitamin E

Topics: Ascorbic Acid; beta Carotene; Blood Pressure; Body Composition; Carotenoids; Colonic Neoplasms; Diet; Female; Humans; Life Style; Lipids; Lung Neoplasms; Male; Neoplasms; Prospective Studies; Risk; Smoking; Stomach Neoplasms; Vitamin B Complex; Vitamin E; Vitamins

Sera were collected in a high-risk area for stomach cancer in Colombia from 857 residents who had been gastroscoped. The levels of 6 micronutrients (retinol, beta-carotene, ascorbic acid, vitamin E, prealbumin, retinol-binding protein) were measured and the mean values correlated with the presence of gastric pathology thought to represent precursors of stomach cancer. Two micronutrients showed important variations in mean levels by gastric pathology: beta-carotene and vitamin E. Beta-carotene levels were low in patients with dysplasia, but no differences were detected for retinol levels.

Topics: Adolescent; Adult; Ascorbic Acid; beta Carotene; Carotenoids; Colombia; Female; Gastric Mucosa; Humans; Male; Middle Aged; Prealbumin; Precancerous Conditions; Retinol-Binding Proteins; Risk; Stomach Neoplasms; Vitamin A; Vitamin E; Vitamins

In south Louisiana, 391 recently diagnosed gastric cancer patients and an equal number of controls were interviewed. Questions asked covered residential and occupational histories, environmental exposures, tobacco use, diet, alcohol consumption, and pertinent demographic characteristics. Elevated relative risks were found for use of tobacco and alcohol products. Diet was found to be the main determinant of gastric cancer risk in south Louisiana. Both dietary patterns and dietary risk factors differed for blacks and whites, although fruits as a group and dietary vitamin C were found to exert strong protective effects for both blacks and whites. Consumption of smoked foods and homemade or home-cured meats increased risk of gastric cancer for blacks but not for whites. The findings are discussed in the light of the prevailing etiologic hypotheses.

Topics: Adult; Aged; Alcohol Drinking; Ascorbic Acid; Black People; Diet; Female; Humans; Income; Louisiana; Male; Middle Aged; Models, Biological; Occupations; Risk; Smoking; Socioeconomic Factors; Sodium Chloride; Stomach Neoplasms; White People

As part of an ongoing cohort study of gastric cancer precursors in Nariño, Colombia, blood levels of ascorbic acid, vitamin E, retinol, pre-albumin, retinol binding protein and carotenoids were measured and correlated with histopathologic findings of gastric biopsies. Carotene levels in both sexes and vitamin E levels in males were significantly lower in subjects with gastric dysplasia than in subjects with normal mucosa and subjects with less advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia). No other significant correlations were found.

Topics: Adolescent; Adult; Age Factors; Aged; Ascorbic Acid; Carotenoids; Female; Gastric Mucosa; Gastritis; Humans; Male; Metaplasia; Middle Aged; Prealbumin; Retinol-Binding Proteins; Sex Factors; Stomach Diseases; Stomach Neoplasms; Vitamin A; Vitamin E; Vitamins

Mutagenic activity, ascorbic acid levels and pH were measured in fasting gastric juice from eight patients given oral supplements of vitamin C (1 g qid X 7 days). Supplementation significantly reduced mutagenic activity and increased intragastric ascorbate levels without altering gastric pH. These results demonstrate for the first time the relation between intragastric ascorbate levels, mutagenic activity and oral supplements of vitamin C. The findings are discussed in relation to the possible chemoprevention of gastric cancer.

Topics: Adult; Aged; Ascorbic Acid; Female; Gastric Acidity Determination; Gastric Juice; Humans; Male; Middle Aged; Mutagens; Stomach Neoplasms

The modifying effects of 3 antioxidants, sodium L-ascorbate (SA), ascorbic acid (AA) and sodium erythorbate (SE) on two-stage gastric carcinogenesis in F344 rats initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated. Administration of 5% SE in the diet significantly decreased the incidence of dysplasia of the pylorus and, more marginally the incidence of papilloma of the forestomach, whereas administration of 5% and 1% SA and 5% AA in the diet was not associated with effect. These results suggest that SE exerts a weak inhibitory effect on gastric carcinogenesis.

Topics: Animals; Ascorbic Acid; Body Weight; Cocarcinogenesis; Male; Methylnitronitrosoguanidine; Rats; Rats, Inbred F344; Stomach Neoplasms; Urinary Bladder Neoplasms

Topics: Animals; Ascorbic Acid; Immunity, Cellular; Immunocompetence; Leukocyte Count; Male; Methylcholanthrene; Mice; Stomach Neoplasms; T-Lymphocytes

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; Carcinoma; Combined Modality Therapy; Female; Fluorouracil; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Metastasis; Postoperative Care; Stomach Neoplasms

Levels of certain metabolites of peroxidation of lipids such as diene conjugates malonic dialdehyde, ascorbic acid, dehydroascorbic acid and diketogulonic acid were compared in 39 cases of gastric ulcer, 25 patients with gastric cancer and 14 healthy subjects. Diene conjugates and malonic dialdehyde levels appeared to be increased in cases of gastric ulcer and cancer. This was matched by a decrease in ascorbic acid and dehydroascorbic acid levels. Ulcer patients revealed enhanced diketogulonic acid concentration.

Topics: 2,3-Diketogulonic Acid; Adenocarcinoma; Aged; Ascorbic Acid; Dehydroascorbic Acid; Female; Humans; Lipid Peroxides; Male; Malondialdehyde; Middle Aged; Stomach Neoplasms; Stomach Ulcer

The promoting effects of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) and sodium L-ascorbate on two-stage carcinogenesis initiated with methylnitrosourea (MNU) in F344 male rats were investigated. Animals were given injections of MNU (20 mg/kg ip) twice a week for 4 weeks, and then basal diet containing 2% BHA, 1% BHT or 5% sodium L-ascorbate for the next 32 weeks. Administration of BHA, BHT or sodium L-ascorbate in the diet significantly increased the incidences per group and numbers per rat of papilloma and papillary or nodular hyperplasia of the urinary bladder, and BHA and BHT also increased the number of cancers per rat. Furthermore BHA significantly increased the incidences of cancer and papilloma in the forestomach of rats initiated with MNU, whereas treatment with BHA alone was associated with papilloma but no carcinoma development in the rat forestomach. The incidence of adenoma, but not adenocarcinoma, of the thyroid was significantly increased by treatment with MNU plus BHT. These results show that BHA, BHT and sodium L-ascorbate have promoting activities on urinary bladder carcinogenesis in rats initiated with MNU, and that BHA also has a promoting effect on forestomach carcinogenesis after initiation with MNU.

Topics: Animals; Anisoles; Ascorbic Acid; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Hyperplasia; Male; Methylnitrosourea; Papilloma; Rats; Rats, Inbred F344; Stomach; Stomach Neoplasms; Urinary Bladder Neoplasms

Administration to rats of ascorbate with morpholine and nitrite was previously shown to inhibit the liver tumor production and to enhance the induction of forestomach tumors, as compared to treatment with morpholine and nitrite. In a repetition of this experiment, 10 g morpholine/kg in the diet and 2 g sodium nitrite/liter in the drinking water were administered for life to male MRC-Wistar rats without (group 1) or with (group 2) 22.7 g sodium ascorbate/kg in the diet. Group 3 was untreated. Group 2 showed a lower liver tumor incidence with a longer latency than group 1, indicating a 78% inhibition by ascorbate of in vivo N-nitrosomorpholine (NMOR) formation. The incidence of forestomach papillomas was 3% in group 1, 38% in group 2, and 8% in group 3. The difference between groups 1 and 2 was not significant due to the shorter life-span of group 1. Group 1 and especially group 2 had more forestomach hyperplasia and hyperkeratosis than group 3. Ascorbate might have enhanced induction of these lesions because of an action synergistic with that of NMOR. However, it is most likely that the lowered NMOR dose and concomitantly increased survival produced by the ascorbate were solely responsible for the increased incidence of forestomach papillomas and other lesions in group 2.

Topics: Animals; Ascorbic Acid; Diet; Drug Interactions; Esophagus; Hyperplasia; Liver Neoplasms; Male; Morpholines; Nitrites; Nitrosamines; Papilloma; Rats; Sodium Nitrite; Stomach; Stomach Neoplasms; Time Factors

An analysis of 1315 cases of gastric cancer from the records of the Ministry of Public Health, San José, Costa Rica between 1977 and 1980 showed important geographical differences in the incidence, and especially in relation to the sex ratio, age structure and migratory patterns. Rates of incidence ranged between 12.6 and 153.2 per 100,000 inhabitants in men and 10.6 and 56.6 in women. Variations in the incidence of gastric cancer rates were studied in relation to ecological parameters, including certain soil and drinking water characteristics as well as the presence of vitamins A and C in serum. No significant relation was found between gastric cancer rates and the presence of vitamins and of several components in drinking water. However, a multivariate analysis considering nine soil components and pH showed a statistically significant (p less than 0.01) association with pH, K, Zn and Fe, which account for 22% of the variation in the incidence rates. A dynamic and multifactorial model is proposed to explain regional variations in cancer rates, with a tentative application of this model to the results obtained.

Topics: Ascorbic Acid; Consanguinity; Costa Rica; Ecology; Female; Humans; Male; Soil; Stomach Neoplasms; Transients and Migrants; Vitamin A; Water Supply

Topics: Adenocarcinoma; Animals; Antioxidants; Ascorbic Acid; Carcinoma, Squamous Cell; Male; Methylnitronitrosoguanidine; Neoplasms; Rats; Rats, Inbred F344; Sarcoma; Stomach Neoplasms

The effects of the antioxidants, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ethoxyquin (EQ), and sodium L-ascorbate (SA) on two stage chemical carcinogenesis were investigated in male F344 rats initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), N-ethyl-N-hydroxyethylnitrosamine (EHEN), N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) or N-methylnitrosourea (MNU). BHA was given in diet at a dose level of 0.5 or 2.0%, BHT at 1.0%, SA at 5.0% and EQ at 0.8% for 29-51 weeks. Complete autopsy was performed at sacrifice and organs were examined histologically for the presence of preneoplastic and neoplastic lesions. All of the antioxidants tested exerted a positive influence on the development of BBN- or MNU-initiated bladder carcinogenesis. Similarly, these chemicals tended to enhance the appearance of forestomach tumors although the data gained after BHT administration were not significant. In clear contrast, no effect was observed on glandular stomach carcinogenesis and, with the exception of SA, the antioxidants all showed inhibition of the development of preneoplastic and neoplastic lesions in the liver. EQ increased the occurrence of renal adenoma in EHEN-treated rats. Clear differences were observed with respect to the modification of thyroid carcinogenesis after MNU initiation, BHT demonstrating strong promotion activity whereas BHA and SA had no effect. Thus organ specificity, with regard to both direction of modification and to the effects of individual antioxidants was apparent, this intriguing finding offering hope for the development of future experimental approaches for elucidation of the mechanisms underlying chemical carcinogenesis.

Topics: Animals; Antioxidants; Ascorbic Acid; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Ethoxyquin; Kidney Neoplasms; Liver Neoplasms; Methylnitrosourea; Neoplasms, Experimental; Rats; Rats, Inbred F344; Stomach Neoplasms; Urinary Bladder Neoplasms

Published figures for per capita daily levels of nitrate ingestion in the 1970s are compared with gastric cancer mortality estimates for the same period. A strong positive correlation is observed in 12 countries, not only when the data are analyzed as a linear-linear function, as illustrated in this paper, but also when the relationship is analyzed as a function of (nitrate)2. This correlation supports the concept that important components of gastric cancer induction are the in vivo bacterial reduction of nitrate to nitrite and the intragastric formation of mutagenic/carcinogenic nitroso, and possibly nitro compounds. Data are summarized from a recent National Academy of Sciences [1981] study that enumerates by individual dietary sources the mean ingestion of nitrate and nitrite by the United States population at the present time. The ingestion figures are used to calculate the probable current gastric nitrite load in US adults with normal gastric acidity. Similar calculations are provided for past years (1925, 1936-1937, and 1971-1972). Since 1925, there has been an approximately threefold decrease in gastric cancer mortality in the US, and this decline is paralleled by an approximately fourfold decrease in average gastric nitrite load. The excessive ingestion of nitrate/nitrite in the US in past years is attributed to the very high content of nitrate and nitrite in cured meats. Several ways compatible with current US farming and marketing practices that are capable of reducing the gastric nitrite load even further are pointed out.

Topics: Animals; Ascorbic Acid; Carcinogens; Food Analysis; Food Preservatives; Global Health; Humans; Nitrates; Nitrites; Nitrosamines; Stomach Neoplasms

The biological mode of action of tumor promoters, exemplified by the phorbol esters, is a subject of intensive study in a number of laboratories. A few investigators have recently begun to examine the role of dietary nutrients in tumor promotion, but the available data are sparse and interpretation difficult. A few examples are provided to indicate that some nutrients may be important in the promotion of cancer. However, the fine dividing line between effects on initiation or on promotion, so clearly shown in the mouse two-stage skin cancer model, is not so clear as yet in models used for studies in nutritional carcinogenesis. The animal models for these studies have been primarily rats, mice and hamsters. These have shown that nutrients which appear to have promotion activity are zinc deficiency and 13-cis-retinoic acid for the esophagus; vitamin A deficiency and lipotrope deficiency for the forestomach, unsaturated fat and vitamin A deficiency for liver and colon, lipotrope deficiency for the liver; selenium for the liver. It is probably more correct at this early stage of investigation to consider the effects of nutrients acting either during the time of exposure to the carcinogen, or, after such exposure and when no detectable carcinogen is found in the animals tissues, rather than as promoters in the strict sense.

Topics: Animals; Ascorbic Acid; Carcinogens; Cocarcinogenesis; Colonic Neoplasms; Cricetinae; Diet; Disease Models, Animal; Esophageal Neoplasms; Gastrointestinal Neoplasms; Liver Neoplasms; Mice; Neoplasms, Experimental; Pancreatic Neoplasms; Rats; Stomach Neoplasms; Zinc

Topics: Ascorbic Acid; Carcinogens; Female; Free Radicals; Humans; Leukocytes; Lung Neoplasms; Male; Neoplasms; Nicotiana; Plants, Toxic; Smoke; Smoking; Sodium; Stomach Neoplasms; Vascular Diseases; Vitamin A; Vitamin E

The long-term maintenances of guinea pigs on diets with (a) lack of vitamin C, (b) lack of lysine, methionine and threonine or (c) with a deficiency of all the above nutrients led to the development of oesophageal hyperplasia and atrophic gastritis. These dietary insufficiences were found to favour oesophageal and gastric cancer production by NPIP with a greatly shortened tumour induction time. It seems likely that the observed features of NPIP carcinogenesis depend on the alteration of the chemistry and biochemistry of these organs provoked by the low intake of the above-mentioned nutrients.

Topics: Amino Acids; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinogens; Esophageal Neoplasms; Female; Guinea Pigs; Male; Neoplasms, Experimental; Nitrosamines; Probability; Stomach Neoplasms

Endogenous formation of N-nitrosoproline (NPRO) was demonstrated by monitoring its excretion in the urine of a male volunteer who had ingested vegetable juice, as a source of nitrate, and proline. The resulting NPRO was analyzed after derivatization by combined gas-liquid chromatography thermal energy analysis. The amount of total NPRO excreted in the urine was found to be proportional to the proline dose and increased exponentially with the nitrate dose ingested. Neither nitrate nor proline, when taken alone, led to a detectable increase in NPRO in urine. The amounts of NPRO formed (as estimated from the amounts excreted within 24 hr) after dosing 325 mg nitrate (NO3-) followed by 500 mg proline, ranged from 16.6 to 30.0 (mean, 23.3) micrograms per person. The simultaneous intake of ascorbic acid or alpha-tocopherol inhibited nitrosation of proline in vivo. Monitoring of NPRO or other N-nitroso compounds excreted in the urine thus appears to be a suitable procedure for estimating daily human exposure to endogenously formed N-nitroso compounds.

Topics: Ascorbic Acid; Diet; Humans; Male; Monitoring, Physiologic; Nitrates; Nitrosamines; Proline; Risk; Stomach Neoplasms; Vegetables; Vitamin E

Stomach cancer incidence rates were compared among four groups: Japanese in Japan, Japanese in Hawaii, Caucasians in Hawaii, and all American whites. The highest rates at all ages occurred in the Japan Japanese, followed next by the Hawaii Japanese. Hawaii Caucasians tended to have similar age-specific rates to American whites in general. When the Japanese and Caucasians in Hawaii were divided by place of birth, the Japanese migrants to Hawaii had higher age-adjusted incidence rates than the Japanese born in Hawaii, while the Caucasian migrants to Hawaii (chiefly from the United States mainland) had lower rates than the Caucasians born in Hawaii. Examination of dietary data in relation to the place-of-birth-specific incidence rates showed positive association of stomach cancer with consumption of rice, pickled vegetables, and dried/salted fish, and a negative association with vitamin C intake. The results are consistent with the particular hypothesis that stomach cancer is caused by endogenous nitrosamine formation from dietary precursors, and that vitamin C may protect against the disease.

Topics: Aged; Animals; Ascorbic Acid; Asian People; Diet; Dietary Carbohydrates; Female; Fishes; Food Preservation; Hawaii; Humans; Japan; Male; Middle Aged; Oryza; Sex Factors; Sodium Chloride; Stomach Neoplasms; United States; Vegetables; White People

Topics: Adenocarcinoma; Animals; Ascorbic Acid; Biotransformation; Diet; Fish Products; Male; Mutagens; Neoplasms, Experimental; Nitrites; Rats; Salmonella typhimurium; Stomach Neoplasms

The dominant role of the physical and chemical environment in the development of cancer is challenged. Analyses of the etiology of skin, bladder, respiratory and gastric cancers are presented which demonstrate the considerable extent to which one's health status may modify the initiation and promotion of environmentally associated cancers. It is concluded that although environmental factors may initiate and/or promote 85 to 90 percent of all cancers this is misleading since it neglects the critical role of the individual's health status as a factor modifying carcinogenesis.

Topics: Ascorbic Acid; Benzopyrenes; Carcinogens, Environmental; Carcinoma, Bronchogenic; Diet; Humans; Hydrocarbons; Neoplasms; Neoplasms, Radiation-Induced; Racial Groups; Riboflavin; Skin Neoplasms; Smoking; Stomach Neoplasms; Ultraviolet Rays; Urinary Bladder Neoplasms; Vitamin A

Topics: Animals; Ascorbic Acid; Carcinogens, Environmental; Dose-Response Relationship, Drug; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Microsomes, Liver; Mutagens; Mutation; Nitrosamines; Rats; Salmonella typhimurium; Spermidine; Stomach Neoplasms

Topics: Ascorbic Acid; Humans; Nitrosamines; Stomach Neoplasms

By the Salmonella typhimurium test, extracts of Japanese raw fish treated in the laboratory with nitrite showed mutagenic activity which is prevented by addition of ascorbate. Extracts from similarly treated beef and hot dogs were nonmutagenic. The data conform to a working concept that the high stomach cancer incidence in Japanese and certain other populations may be due to specific dietary factors of an alkylnitrosamide type.

Topics: Animals; Ascorbic Acid; Diet; Fishes; Food Preservatives; Humans; Mutation; Nitrites; Nitroso Compounds; Salmonella typhimurium; Stomach Neoplasms

Topics: Adult; Ascorbic Acid; Cardia; Esophageal Neoplasms; Female; Flavonoids; Humans; Middle Aged; Oxygen Inhalation Therapy; Stomach Neoplasms; Uterine Cervical Neoplasms; Vitamin B Complex; Vitamins

Groups of male MRC Wistar rats were treated for 2 years either with morpholine (10 g/kg food) together with sodium nitrite (3 g/l drinking water) or with N-nitrosomorpholine (NM, 0.15g/l drinking water). In both cases, a group of rats was given sodium ascorbate (22.7 g/kg food) in addition to these treatments. When ascorbate was present, the liver tumors induced by morpholine and nitrite showed a 1.7-fold longer induction period, a slightly lower incidence, and an absence of metastases in the lungs, indicating that ascorbate had inhibited the in vivo formation of NM. Ascorbate did not affect liver tumor induction by the performed NM. The group treated with morpholine, nitrite, and ascorbate had a 54% incidence of forestomach tumors, including an 18% incidence of squamous cell carcinomas, possibly because ascorbate promoted NM action in this organ.

Topics: Animals; Ascorbic Acid; Drug Interactions; Liver Neoplasms; Male; Morpholines; Neoplasms, Experimental; Nitrites; Nitroso Compounds; Rats; Stomach Neoplasms

Ascorbic acid metabolism is associated with a number of mechanisms known to be involved in host resistance to malignant disease. Cancer patients are significantly depleted of ascorbic acid, and in our opinion this demonstrable biochemical characteristic indicates a substantially increased requirement and utilization of this substance to potentiate these various host resistance factors. The results of a clinical trial are presented in which 100 terminal cancer patients were given supplemental ascorbate as part of their routine management. Their progress is compared to that of 1000 similar patients treated identically, but who received no supplemental ascorbate. The mean survival time is more than 4.2 times as great for the ascorbate subjects (more than 210 days) as for the controls (50 days). Analysis of the survival-time curves indicates that deaths occur for about 90% of the ascorbate-treated patients at one-third the rate for the controls and that the other 10% have a much greater survival time, averaging more than 20 times that for the controls. The results clearly indicate that this simple and safe form of medication is of definite value in the treatment of patients with advanced cancer.

Topics: Adult; Aged; Ascorbic Acid; Breast Neoplasms; Bronchial Neoplasms; Colonic Neoplasms; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Rectal Neoplasms; Stomach Neoplasms; Terminal Care; Urinary Bladder Neoplasms

The formation of nitrite from nitrate was studied in potatoes incubated at room temperature. After 24 hours of incubation at 25 degrees, 112 ppm and 373 ppm of nitrite formed in homogenized cooked potatoes containing 284 ppm and 584 ppm of nitrate, respectively. In homogenized fresh potatoes incubated at 21 degrees and containing 284 ppm of nitrate, 103 ppm of nitrate formed within 24 hours. During the period of nitrite formation, nitrate levels decreased sharply, indicating that reduction of nitrate to nitrite occurred. Incubation at 2 degrees completely prevented nitrite formation in all cases. The formation of methylnitrosourea from added methylurea and nitrite was observed in potato incubated under simulated gastric conditions (37 degrees, pH 1.5). An ascorbate-nitrite mole ratio of 4 gave a 93% inhibition of methylnitrosourea formation. Ascorbate reacted directly with nitrite in potato incubated under identical conditions, yielding a 43% decrease in nitrite concentration. Ascorbate did not react with methylurea or the product, methylnitrosourea.

Topics: Ascorbic Acid; Humans; Methylnitrosourea; Methylurea Compounds; Models, Biological; Nitrates; Nitrites; Plants; Stomach Neoplasms; Vegetables

We have developed the working hypothesis that gastric cancer in man may result from the in vivo nitrosation in the stomach of as yet unknown substrates, with the production of alkylinitrosamides. We have established that a source of the nitrite required for the nitrosation was the reduction of nitrate in foods. Nitrate could be derived from its deliberate addition to food as a preservative, from drinking water, and from foods grown in nitrate-rich soils. The reduction of nitrate does not occur at 2-4 degrees, accounting for the decline in gastric cancer in countries and regions where means of refrigerated food storage have been introduced. Future research includes the search for the substrates, presumably in the form of alkylamides, in some foods typically consumed in high-risk regions.

Topics: Ascorbic Acid; Carcinogens; Diet; Food Preservation; Humans; Nitrates; Nitrites; Nitrosamines; Oxidation-Reduction; Stomach Neoplasms; Temperature

In a study of the vitamin C status of 50 patients with malignant disease, 46 had leucocyte levels less than the lower limit of the normal range (18-50,μg/10(8) W.B.C.) and of these 30 had very low levels (< 12.5 μg/10(8) W.B.C.). Physical signs compatible with subclinical scurvy were frequently recorded and there was a significant decrease in capillary fragility in those with the lowest levels. Most patients had an inadequate dietary intake of ascorbic acid-containing foods and this was felt to be the major factor in producing the vitamin depletion.

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Bronchial Neoplasms; Capillary Fragility; Colonic Neoplasms; Diet; Humans; Leukocytes; Lymphatic Diseases; Neoplasms; Rectal Neoplasms; Scurvy; Stomach Neoplasms

Topics: Administration, Oral; Ascorbic Acid; Breast Neoplasms; Carcinoma; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Evaluation; Drug Stability; Female; Fibrosarcoma; Humans; Injections, Intravenous; Neoplasms; Papilloma; Rectal Neoplasms; Stomach Neoplasms; Time Factors; Urinary Bladder Neoplasms

Topics: Adult; Age Factors; Aged; Animals; Ascorbic Acid; Aspirin; Diet Therapy; Drainage; Female; Humans; Infusions, Parenteral; Male; Middle Aged; Milk; Peptic Ulcer; Potassium; Pyloric Stenosis; Sex Factors; Sodium Chloride; Stomach Neoplasms; Time Factors

Topics: Ascorbic Acid; Female; Glucose; Humans; Injections, Intravenous; Male; Middle Aged; Nicotinic Acids; Portal System; Pyridoxine; Stomach Neoplasms; Thiamine; Vitamins

Topics: Acidosis; Adult; Aged; Ascorbic Acid; Female; Glucose; Humans; Insulin; Intestinal Neoplasms; Lung Neoplasms; Male; Middle Aged; Ovarian Neoplasms; Premedication; Pyridoxine; Stomach Neoplasms; Thiamine; Thiamine Pyrophosphate; Uterine Neoplasms

Topics: Acute Disease; Ascorbic Acid; Blood Transfusion; Diet; Diet Therapy; Duodenal Ulcer; Endoscopy; Esophageal and Gastric Varices; Gastritis; Gastrointestinal Hemorrhage; Hematemesis; Hernia, Diaphragmatic; Humans; Melena; Myocardial Infarction; Peptic Ulcer Hemorrhage; Radiography; Stomach Neoplasms; Vagotomy; Vitamin K

Topics: Ascorbic Acid; Blood; Carcinoma; Catalase; Conductometry; Dialysis; Edetic Acid; Erythrocytes; Ethylmaleimide; Hemolysis; Hot Temperature; Humans; Kidney; Liver; Lung Neoplasms; Male; Neoplasms; Prostatic Neoplasms; Stomach Neoplasms; Tissue Extracts; Triazoles

Topics: Abdomen; Aged; Antiemetics; Ascorbic Acid; Bismuth; Carcinoma, Basal Cell; Diverticulum; Duodenal Diseases; Epididymitis; Gastrectomy; Humans; Liver Neoplasms; Male; Neoplasm Metastasis; Pain; Stomach Neoplasms; Tracheotomy

Topics: Ascorbic Acid; Benzopyrenes; Food Analysis; Humans; Iceland; Nutrition Surveys; Retrospective Studies; Sodium Chloride; Stomach Neoplasms

Topics: Ascorbic Acid; Carcinogens; Citrus; Dietary Fats; Fruit; Humans; Intestinal Neoplasms; Neoplasms; Netherlands; Nutrition Surveys; Nutritional Status; Stomach Neoplasms