ascorbic-acid and Precancerous-Conditions

Squamous cell carcinoma of the oral cavity has long been seen as an attractive candidate for chemoprevention strategies. Because of the poor out-comes associated with the disease, the presence of identifiable premalignant lesions, and the failure of local preventive therapies, such as surgery, many investigators have hoped to find an effective chemopreventive compound. Initial enthusiasm surrounding high-dose retinoids gave way to concerns regarding toxicity and short duration of response. Although many of the other agents discussed above have shown promise, as yet none have been proven safe and effective in large-scale randomized trials. Much has been learned,however, about the molecular process of oral carcinogenesis from studies of these agents. Ongoing and future studies of chemopreventive agents in oral cancer hopefully will be able to exploit our expanding knowledge of these molecular pathways.

Topics: Antineoplastic Agents; Ascorbic Acid; Carcinoma, Squamous Cell; Drugs, Chinese Herbal; Flavonoids; Folic Acid; Humans; Mouth Neoplasms; Precancerous Conditions; Retinoids; Selenium; Vitamin A; Vitamin E

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

Epidemiologic evidence on the relation between nutrition and cervical cancer is reviewed. Cervical cancer is the leading cancer among women in many developing countries, and remains a major public health problem worldwide. This review of nutritional research on cervical neoplasia encompasses the range of epithelial abnormalities from early preneoplastic lesions to invasive cancer. Identified risk factors for cervical neoplasia suggest a multifactorial etiology with several cancer-associated human papillomaviruses (HPV) as the central cause. Studies of nutritional predictors of cervical neoplasia to date, however, have been limited by inadequate HPV measures, which compromise the interpretations of findings. Current research using accurate measures of HPV will be most revealing. Nonetheless, agreement in findings from previous studies suggest a role for nutritional factors in some or all stages of cervical neoplasia. Low vitamin C and carotenoid status are associated fairly consistently with both cervical cancer and precursors, whereas results for vitamin E status are less consistent. The effect of folate status may be restricted to early preneoplastic cervical lesions and not to more advanced disease. Current research is addressing nutritional influences on HPV infection and persistence and on progression of cervical disease. Limitations and recommendations for future research directions are discussed in light of methodologic issues related to nutritional and HPV research.

Topics: Ascorbic Acid; Carotenoids; Developing Countries; Disease Progression; Female; Folic Acid; Humans; Nutritional Physiological Phenomena; Papillomaviridae; Papillomavirus Infections; Precancerous Conditions; Public Health; Risk Factors; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamin E

Epidemiological studies have shown that diets rich in one or more antioxidant nutrients may reduce the risk of cancers of the lung, uterine cervix, mouth, and gastrointestinal tract. Study of premalignant lesions offers a comparatively expedient approach to identifying and evaluating the efficacy of the cancer chemopreventive components of foods. Some recent findings suggest roles for beta-carotene and/or vitamin C in reversing or reducing the risk of cervical dysplasia and oral leukoplakia. There are some indications that vitamin C and beta-carotene may reduce the risk of atrophic gastritis and gastric cancer. Additional epidemiological and molecular biology studies and clinical intervention trials using premalignant lesions as the marker of specific cancer risks should become an important component of future research in the area of cancer chemoprevention.

Topics: Ascorbic Acid; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; Diet; Female; Humans; Neoplasms; Precancerous Conditions; Vitamin E

Topics: Adenoma; Ascorbic Acid; Carcinoma; Cytodiagnosis; Glycogen; Glycosaminoglycans; Goiter, Nodular; Histocytochemistry; Humans; Hyperplasia; Karyometry; Precancerous Conditions; Thyroid Gland; Thyroid Neoplasms; Thyroiditis, Autoimmune

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

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

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

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

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

A double-blind, placebo-controlled, randomized, factorial study using a daily oral administration of 30 mg beta-carotene and/or 500 mg vitamin C was conducted in 141 women with colposcopically and histologically confirmed minor squamous atypia or cervical intra-epithelial neoplasia (CIN) I. Over approximately 2 years of follow-up, 43 lesions regressed to normal and 13 progressed to CIN II. The regression rate was slightly higher, but not significantly so, in those randomized to beta-carotene compared to no beta-carotene (hazard ratio = 1.58, 95% CI: 0.86-2.93, P = 0.14) and slightly lower, but not statistically significant, for those randomized to vitamin C compared to no vitamin C (hazard ratio = 0.65, 95% CI: 0.35-1.21, P = 0.17). In a model with no interaction, the progression rate was slightly higher in those randomized to beta-carotene (hazard ratio = 1.75, 95% CI: 0.57-5.36, P = 0.32) and also in those randomized to vitamin C (hazard ratio = 2.40, 95% CI: 0.74-7.80, P = 0.13). Neither of these were statistically significant. However, there was some evidence of an interaction effect of the two compounds on the progression rate (P = 0.052), with seven of the progressed lesions occurring in those randomized to both vitamins compared to a total of six in the three other groups. The currently available evidence from this and other trials suggests that high doses of these compounds are unlikely to increase the regression or decrease the progression of minor atypia and CIN I.

Topics: Adult; Antioxidants; Ascorbic Acid; beta Carotene; Disease Progression; Double-Blind Method; Female; Follow-Up Studies; Humans; Precancerous Conditions; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

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

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

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

Background: Chemoprevention refers to the use of specificnatural or synthetic chemical agents to suppress the\ development and progression to carcinoma. The purpose of this study was to assess the effect of aspirin, vitamin C\ or zinc on the metallothionein (MT) mRNA gene expression as well as MT protein content byimmunohistochemistry\ andradioimmunoassay (RIA) in 1, 2-dimethyl hydrazine (DMH) induced cancerous colonic tissuein rats. Methods:\ Rats were randomly divided into three groups, group 1 (aspirin), group 2 (vitamin C) group 3 (zinc), each of which\ was further sub divided into two groups and given subcutaneous injections of DMH (30 mg/kg body weight) twice a\ week for 3 months and sacrificed at either 4 months (A-precancer model) or at 6 months (B-cancer model).The control\ groups were administered 0.5 ml saline subcutaneously. All the 3 groups were simultaneouslyadministered aspirin,\ vitamin Cor zinc supplement respectively from the beginning till the end of the study. Results: It was observed that\ rats co-treated with aspirin, vitamin C or zinc resulted in a significant increase in the colonic MT mRNA expression in\ the precancer and cancer model as compared to the saline only controls. MT protein expression showed a 60%, 64%\ and 78% immunopositivity in the co-treated groups respectively.The mean MT content in the precancer and the cancer\ model was restored to near normal levels in all the three co-treated groups. Conclusion: These results suggest that\ co-administration of aspirin, vitamin C or zinc resulted in a significant increase in MT mRNA gene expression, MT\ protein expression and MT protein content which could possibly be one of the reasons for a chemo protective effect\ against progression to colonic cancer in a chemically induced DMH model in rat.Zinc supplement had a greater effect\ on metallothionein expression than aspirin or vitamin C.

Topics: 1,2-Dimethylhydrazine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Aspirin; Colon; Colonic Neoplasms; Dietary Supplements; Metallothionein; Precancerous Conditions; Rats; Rats, Wistar; Trace Elements; Vitamins; Zinc

Asiatic acid (AA), a pentacyclic triterpenoid, derived from the tropical medicinal plant Centella asiatica is known to exhibit numerous pharmacological properties. We hypothesized that AA will have chemopreventive potential against 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis in male Wistar rats. Rats were arbitrarily divided into six groups. Group I rats were processed as control. Group II rats received AA (8 mg/kg b.w., p.o.) and groups III-VI rats received subcutaneous injections of DMH (20 mg/kg b.w.) once a week, for the first four weeks. In addition, groups IV-VI rats received AA at the doses of 2, 4 and 8 mg/kg b.w., respectively, for 16 weeks. Our results discovered that supplementation with AA to the DMH-exposed rats significantly decreased the incidence of polyps and Aberrant crypt foci (ACF) as compared to the DMH-alone-exposed rats. Moreover, in the AA-supplemented DMH-exposed rats, we ascertained increased activities of the antioxidants and decreased levels of lipid peroxidation (LPO) in the liver and circulation and enhanced levels of both LPO and antioxidants in the colon, which were altered in the DMH-alone-exposed rats. Furthermore, we also observed altered activities of vitamins C and E and biotransforming enzymes in DMH-alone-exposed rats, which were reversed on AA supplementation. All the observations were supported by our histological findings. Thus, we can conclude that, AA could be used as an effective chemopreventive agent against DMH-induced colon carcinogenesis.

Topics: 1,2-Dimethylhydrazine; Animals; Anticarcinogenic Agents; Ascorbic Acid; Biotransformation; Catalase; Colon; Colonic Neoplasms; Dose-Response Relationship, Drug; Male; Oxidative Stress; Pentacyclic Triterpenes; Precancerous Conditions; Rats, Wistar; Superoxide Dismutase; Vitamin E

The objectives of this study are to analyze oxidative DNA and lipid damage using salivary 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and vitamins C and E in oral lichen planus lesions, oral leukoplakia, oral submucous fibrosis, oral squamous cell carcinoma (SCC), and controls and to determine the value of salivary biomarkers in the diagnosis of oral pre-cancer and cancer patients.. Unstimulated saliva was collected from a group of patients diagnosed with 40 oral squamous cell carcinoma (OSCC), 40 oral lichen planus lesions, 40 oral leukoplakia, 40 oral submucous fibrosis, and from a control group of healthy age- and gender-matched individuals. Salivary 8-OHdG, MDA, and vitamins C and E were measured.. Squamous cell carcinoma and pre-cancer patients showed significantly higher levels of salivary 8-OHdG and MDA and lower levels of vitamins C and E when compared to levels in healthy normal subjects. The specificity and sensitivity of the combination of 8-OHdG, MDA, vitamin C, and vitamin E are high for the diagnosis of oral pre-cancer and SCC compared to an individual biomarker approach using either 8-OHdG, MDA, or vitamin C and vitamin E independently.. This study indicates the presence of oxidative DNA and lipid damage in pre-cancerous and SCC patients. It is postulated that the mechanism may have a significant link to carcinogenesis in oral cancer. Detection of salivary 8-OHdG, MDA, vitamin C, and vitamin E can act as suitable diagnostic biomarkers of oral pre-cancer and cancer.. Of clinical importance is that salivary 8-OHdG, MDA, vitamin C, and vitamin E could play a significant role in oral cancer and pre-cancer patients and could therefore be useful for diagnosis in patients with oral lichen planus lesions, oral leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Ascorbic Acid; Biomarkers; Biopsy; Carcinoma, Squamous Cell; Case-Control Studies; Deoxyguanosine; Female; Free Radicals; Humans; Leukoplakia, Oral; Lichen Planus, Oral; Male; Malondialdehyde; Middle Aged; Mouth Neoplasms; Oral Submucous Fibrosis; Precancerous Conditions; Risk Factors; Saliva; Sensitivity and Specificity; Vitamin E

Chemoprotection refers to the use of specific natural or synthetic chemical agents to suppress or prevent the progression to cancer. The purpose of this study is to assess the protective effect of aspirin, vitamin C or zinc in a dimethyl hydrazine (DMH) colon carcinoma model in rats and to investigate the effect of these supplements on changes associated with colonic zinc status. Rats were randomly divided into three groups, group 1 (aspirin), group 2 (vitamin C) and group 3 (zinc), each being subdivided into two groups and given subcutaneous injection of DMH (30 mg/kg body wt) twice a week for 3 months and sacrificed at 4 months (A-precancer model) and 6 months (B-cancer model). Groups 1, 2, 3 were simultaneously given aspirin, vitamin C, or zinc supplement respectively from the beginning till the end of the study. It was observed that 87.5% of rats co-treated with aspirin or vitamin C showed normal colonic histology, along with a significant decrease in colonic tissue zinc at both time points. Rats co-treated with zinc showed 100% reduction in tumor incidence with no significant change in colonic tissue zinc. Plasma zinc, colonic CuZnSOD (copper-zinc superoxide dismutase) and alkaline phosphatase activity showed no significant changes in all 3 cotreated groups. These results suggest that aspirin, vitamin C or zinc given separately, exert a chemoprotective effect against chemically induced DMH colonic preneoplastic progression and colonic carcinogenesis in rats. The inhibitory effects are associated with maintaining the colonic tissue zinc levels and zinc enzymes at near normal without significant changes.

Topics: 1,2-Dimethylhydrazine; Alkaline Phosphatase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Apoptosis; Ascorbic Acid; Aspirin; Blotting, Western; Carcinogens; Cell Proliferation; Colonic Neoplasms; Dietary Supplements; Disease Models, Animal; Precancerous Conditions; Rats; Rats, Wistar; Superoxide Dismutase; Trace Elements; Zinc

Extensive research within the past half-century has indicated that curcumin (diferuloylmethane), a yellow pigment in curry powder, exhibits anti-oxidant, anti-inflammatory, and pro-apoptotic activities. We investigated whether the anti-pre-cancer activities assigned to curcumin are mediated through an anti-oxidant and DNA-protecting mechanism. Patients with oral leukoplakia, oral submucous fibrosis or lichen planus, and healthy individuals (n = 25 for each group) aged 17-50 years were selected. Salivary and serum oxidative markers such as malonaldehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), vitamins C and E were measured just prior to the intake of curcumin, after one week of curcumin intake and following clinical cure of precancerous lesions. Serum and salivary vitamins C and E showed increases, while MDA and 8-OHdG levels showed decreases in patients with oral leukoplakia, submucous fibrosis and lichen planus after intake of curcumin for all categories of precancerous lesions. The changes in these values were observed to be statistically significant after clinical cure of the disease (P < 0.05). The five-point rating scale for pain, as well as lesion size in oral leukoplakia, submucous fibrosis and lichen planus, improved significantly (P < 0.05). In addition, in submucous fibrosis, mouth opening (P < 0.05) recovered significantly. In oral leukoplakia, submucous fibrosis and lichen planus, the levels of serum and salivary vitamins C and E increased significantly, while MDA and 8-OHdG levels decreased after 131(15), 211(17), and 191(18) days, respectively. Values for serum and salivary vitamins C and E showed a significant decrease in oral leukoplakia, submucous fibrosis and lichen planus, in contrast to healthy individuals, but increased significantly in all groups subsequent to curcumin administration after clinical cure of lesions. Based on these results, we can conclude that curcumin mediates its anti-pre-cancer activities by increasing levels of vitamins C and E, and preventing lipid peroxidation and DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Antioxidants; Ascorbic Acid; Biomarkers; Curcumin; Deoxyguanosine; DNA; DNA Damage; Female; Follow-Up Studies; Free Radical Scavengers; Humans; Leukoplakia, Oral; Lichen Planus, Oral; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Mouth Neoplasms; Oral Submucous Fibrosis; Oxidative Stress; Pain Measurement; Precancerous Conditions; Protective Agents; Saliva; Vitamin E; Young Adult

An estimated 25-40 million of the 127 million people of Bangladesh have been exposed to high levels of naturally occurring arsenic from drinking groundwater. The mitigating effects of diet on arsenic-related premalignant skin lesions are largely unknown.. The purpose of this study was to clarify the effects of the vitamin B group (thiamin, riboflavin, niacin, pyridoxine, and cobalamin) and antioxidants (vitamins A, C, and E) on arsenic-related skin lesions.. We performed a cross-sectional study using baseline data from the Health Effects of Arsenic Longitudinal Study (HEALS), 2000-2002, with individual-level, time-weighted measures of arsenic exposure from drinking water. A total of 14,828 individuals meeting a set of eligibility criteria were identified among 65,876 users of all 5,996 tube wells in the 25-km(2) area of Araihazar, Bangladesh; 11,746 were recruited into the study. This analysis is based on 10,628 subjects (90.5%) with nonmissing dietary data. Skin lesions were identified according to a structured clinical protocol during screening and confirmed with further clinical review.. Riboflavin, pyridoxine, folic acid, and vitamins A, C, and E significantly modified risk of arsenic-related skin lesions. The deleterious effect of ingested arsenic, at a given exposure level, was significantly reduced (ranging from 46% reduction for pyridoxine to 68% for vitamin C) for persons in the highest quintiles of vitamin intake.. Intakes of B-vitamins and antioxidants, at doses greater than the current recommended daily amounts for the country, may reduce the risk of arsenic-related skin lesions in Bangladesh.

Topics: Adult; Antioxidants; Arsenic; Ascorbic Acid; Bangladesh; Cross-Sectional Studies; Environmental Exposure; Female; Humans; Male; Middle Aged; Precancerous Conditions; Risk Factors; Skin Diseases; Vitamin A; Vitamin B Complex; Vitamin E

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

Case-control studies indicate that vitamins C, E, A and carotenoids decrease risk of oral premalignant lesions (OPLs) and oral cancer, but clinical trials have failed to find protective effects of beta-carotene and suggest that vitamin E may increase risk. The authors prospectively evaluated the association between intake of vitamins C, E, A and carotenoids and incidence of OPL. Participants were 42,340 men in the Health Professionals Follow-up Study who provided information on supplement use and diet every 2-4 years by food frequency questionnaire. The authors confirmed 207 clinically or histopathologically diagnosed OPL events occurring between 1986 and 2002 by medical record review. Multivariate-adjusted relative risks (RR) of OPL were calculated with proportional hazards models. Total intake of vitamin C, vitamin A or carotenoids was not significantly associated with OPL risk. Dietary vitamin C was significantly associated with reduced risk (quintile 5 vs. 1, RR = 0.52, 95% CI 0.31-0.85, p(trend) = 0.04), but no association with supplemental vitamin C was observed. Inverse associations were apparent for beta-cryptoxanthin and alpha-carotene intake. No clear relationship emerged with beta-carotene, lycopene or lutein/zeaxanthin. Vitamin E was associated with increased risk (quintile 5 vs. 1, RR = 1.86, 95% CI 1.06-3.19), particularly among current smokers and with supplemental intake (current-smokers, supplement dose tertile 3 vs. 1, RR = 3.07, 95% CI 1.28-7.34, p(trend) = 0.01). For current smokers, beta-carotene also increased risk. Vitamin C from dietary sources, but not supplements, was associated with a reduced risk of OPL. The observed increased risk for current smokers with high vitamin E or beta-carotene intake should be explored further.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Cryptoxanthins; Diet; Humans; Male; Middle Aged; Mouth Neoplasms; Precancerous Conditions; Risk Factors; Smoking; United States; Vitamin A; Vitamin E; Vitamins; Xanthophylls

The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by the availability of suitable laboratory animal models. Here we report that male Hartley guinea pigs treated with cigarette smoke by inhalation twice a day for 28 days developed preneoplastic lung lesions, including bronchial hyperplasia, dysplasia and squamous metaplasia, analogous to those found in human smokers. The lesions were accompanied by increased expression of proliferating cell nuclear antigen and activation of the serine/threonine kinase Akt in the bronchial epithelium. In contrast, no lung lesions were found in guinea pigs ('sham smoked') that were submitted to identical procedures but without cigarettes. Compared with a diet low in vitamin C (50 p.p.m.) and vitamin E (15 p.p.m.), a diet high in vitamin C (4000 p.p.m.) and vitamin E (40 p.p.m.) significantly increased the incidence of these lesions. The inclusion of 1,4-phenylenebis(methylene)selenocyanate (p-XSC), a synthetic chemopreventive organoselenium compound, in the high vitamin C-high vitamin E diet at a level of 15 p.p.m. as selenium appeared to decrease the lesion incidence. Administration of (-)-epigallocatechin gallate, a powerful green tea polyphenolic antioxidant, at 560 p.p.m. in the drinking water had no effect. As in human smokers, levels of ascorbate in blood plasma, lung, liver and the adrenal glands were significantly decreased by cigarette smoke inhalation. These results identify a relevant in vivo laboratory model of cigarette smoke-induced lung cancer, suggest that p-XSC may have activity as a chemopreventive agent against cigarette smoke-induced lung lesions and provide additional evidence that very high dietary levels of certain antioxidants can have co-carcinogenic activity in cigarette smoke-induced lung cancer.

Topics: Animals; Ascorbic Acid; Diet; Enzyme Activation; Guinea Pigs; Immunohistochemistry; Inhalation Exposure; Lung Neoplasms; Nicotiana; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Smoke; Vitamin E

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

When saliva, with its high nitrite content derived from the enterosalivary recirculation of dietary nitrate, meets acidic gastric juice, the nitrite is converted to nitrous acid, nitrosative species, and nitric oxide. In healthy volunteers this potentially mutagenic chemistry is focused at the gastric cardia. We have studied the location of this luminal chemistry in Barrett's patients during acid reflux.. Ten Barrett's patients were studied before and after administration of 2 mmol nitrate. Using microdialysis probes we measured nitrite, ascorbic acid, total vitamin C, and thiocyanate concentrations and pH simultaneously in the proximal oesophagus, Barrett's segment, hiatal sac, proximal stomach, and distal stomach. In a subgroup, real time nitric oxide concentrations were also measured.. During acid reflux, Barrett's segment was the anatomical site with maximal potential for acid catalysed nitrosation, with its median concentration of nitrite exceeding that of ascorbic acid in two of 10 subjects before nitrate and in four of nine after nitrate. Thiocyanate, which catalyses acid nitrosation, was abundant at all anatomical sites. On entering the acidic Barrett's segment, there was a substantial fall in nitrite and the lowest ascorbic acid to total vitamin C ratio, indicative of reduction of salivary nitrite to nitric oxide at this anatomical site. Episodes of acid reflux were observed to generate nitric oxide concentrations of up to 60 muM within the Barrett's segment.. The interaction between acidic gastric refluxate and nitrite rich saliva activates potentially mutagenic luminal nitrosative chemistry within Barrett's oesophagus.

Topics: Aged; Ascorbic Acid; Barrett Esophagus; Esophageal Neoplasms; Esophagoscopy; Female; Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Male; Microdialysis; Middle Aged; Nitrates; Nitric Oxide; Nitrites; Nitrosation; Precancerous Conditions; Saliva; Thiocyanates

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

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

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

The effects of 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), phenylethylisothiocyanate (PEITC), 3-O-ethylascorbic acid, 3-O-dodecylcarbomethylascorbic acid and n-heptadecane-8, 10-dione were analyzed in a rat multiorgan carcinogenesis model. Groups of 15 animals were given a single intraperitoneal (i.p.) injection of diethylnitrosamine and 4 i.p. injections of N-methylnitrosourea as well as N-butyl-N-(4-hydroxybutyl) nitrosamine in the drinking water during the first 2 weeks. Then 4 subcutaneous (s.c.) injections of dimethylhydrazine and 2,2'-dihydroxy-di-n-propylnitrosamine were given in the drinking water over the next 2 weeks for initiation. Test compounds were administered during the initiation or post-initiation periods. The dietary dose was 1% except for n-heptadecane-8, 10-dione and PEITC (0.1%). Complete autopsy was performed at the end of experimental week 28. All 5 compounds reduced the number of lung hyperplasia, particularly PEITC when given during the initiation period. In addition, HTHQ lowered the incidence of esophageal hyperplasia in the initiation period, and of small and large intestinal adenomas in the post-initiation period. However, it also enhanced the development of hyperplasia and papilloma in the forestomach and tongue. PEITC lowered the induction of esophageal hyperplasia, kidney atypical tubules and liver glutathione S-transferase placental form (GST-P)-positive foci when given during the initiation period but enhanced the development of liver GST-P positive foci and urinary bladder tumors in the post-initiation period. Moreover, it induced hyperplasia of the urinary bladder. Our results indicate minor adverse effects for HTHQ in the forestomach and tongue, and demonstrate that PEITC, which inhibits carcinogenesis at the initiation stage in several organs, also exhibits promotion potential in liver and urinary bladder in the post-initiation stage under the present experimental conditions.

Topics: Animals; Anticarcinogenic Agents; Ascorbic Acid; Glutathione Transferase; Hydroquinones; Isothiocyanates; Male; Neoplasm Staging; Neoplasms, Experimental; Organ Specificity; Precancerous Conditions; Rats; Rats, Inbred F344

To investigate the relationship of specific nutrients and food items with oral precancerous lesions among tobacco users.. A population-based case-control study.. Villages in Palitana taluk of Bhavnagar district, Gujarat, India.. An interviewer-administered food frequency questionnaire, developed and validated for this population, was used to estimate nutrient intake in blinded, house-to-house interviews. Among 5018 male tobacco users, 318 were diagnosed as cases. An equal number of controls matched on age (+/- 5 years), sex, village, and use of tobacco were selected.. Odds ratios (OR) from multiple logistic regression analysis controlling for relevant variables (type of tobacco use and economic status).. A protective effect of fibre was observed for both oral submucous fibrosis (OSF) and leukoplakia, with 10% reduction in risk per g day-1 (P < 0.05). Ascorbic acid appeared to be protective against leukoplakia with the halving of risk in the two highest quartiles of intake (versus the lowest quartile: OR = 0.46 and 0.44, respectively; P < 0.10). A protective effect of tomato consumption was observed in leukoplakia and a suggestion of a protective effect of wheat in OSF.. In addition to tobacco use, intake of specific nutrients may have a role in the development of oral precancerous lesions.

Topics: Adult; Ascorbic Acid; Case-Control Studies; Diet; Diet Surveys; Dietary Fiber; Feeding Behavior; Humans; India; Leukoplakia, Oral; Logistic Models; Male; Micronutrients; Middle Aged; Multivariate Analysis; Odds Ratio; Oral Submucous Fibrosis; Plants, Toxic; Precancerous Conditions; Smoking; Solanum lycopersicum; Surveys and Questionnaires; Tobacco, Smokeless; Triticum

Overexpression of cyclin D1 has been implicated in the malignant transformation of a variety of human cancers, including urinary bladder carcinomas. However, few reports have addressed the significance of cyclin D1 overexpression in chemical carcinogenesis in rodents. In the present study, we evaluated the oncogenic potential of cyclin D1 in experimental rat urinary bladder carcinogenesis and its relationships to the oncogenes cyclin E, K-ras, and H-ras as well as tumor suppressor genes p53 and p21WAF1/Cip1. In addition, proliferation status of preneoplastic lesions and tumors was assessed by proliferating cell nuclear antigen immunohistochemistry. Fisher 344 rats were initiated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in the drinking water for 4 weeks and then administered 5% sodium L-ascorbate in diet. Animals were sacrificed at weeks 4, 8, 12, 18, and 24. Preneoplastic lesions such as papillary or nodular hyperplasia and neoplastic lesions of the urinary bladder were observed during carcinogenesis. By immunohistochemical examination, overexpression of cyclin D1 protein was observed in 17% of papillary or nodular hyperplasias, 66% of papillomas, and 69% of transitional cell carcinomas, whereas nuclear accumulation of p53 was observed in none of the preneoplastic lesions and in fewer than 2% of transitional cell carcinomas. Overexpression of cyclin D1 in preneoplastic lesions and tumors was not dependent on the size of the tumors or their proliferation status. Quantitation of mRNA in tumors by multiplex reverse transcription-PCR showed that average mRNA expression of cyclin D1 and cyclin E was increased, whereas average p21WAF1/Cip1 mRNA expression was decreased. More than 2-fold overexpression of cyclin D1 mRNA was observed in 50 and 60% of tumors at weeks 18 and 24, respectively. Localization of cyclin D1 mRNA expression was demonstrated by in situ hybridization, and the results were comparable to immunohistochemistry findings. None of the 25 tumors we examined by PCR-single-strand conformational polymorphism analysis harbored p53 mutations, H-ras mutations, or K-ras mutations. Thus, during the promotion phase of two-stage bladder carcinogenesis, overexpression of cyclin D1 in tumor cells may provide yet another mechanism by which tumors can gain a growth advantage. In contrast, tumors with mutated p53 may not have a growth advantage. Our results suggest that overexpression of cyclin D1 plays a critical role during urinary bladder carcinogenesi

Topics: Animals; Ascorbic Acid; Butylhydroxybutylnitrosamine; Carcinogens; Carcinoma, Transitional Cell; Cell Nucleus; Cyclin D1; Cyclin E; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Hyperplasia; Male; Neoplasm Proteins; Papilloma; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Rats; Rats, Inbred F344; RNA, Messenger; Tumor Suppressor Protein p53; Urinary Bladder; Urinary Bladder 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

We have established an experimental model of oral contraceptive-induced hepatocellular carcinomas (HCCs) in female Wistar rats, revealing that ethynylestradiol (EE) and norethindrone acetate have actions as both initiators and promoters. The present time-sequence study was undertaken to clarify the role of free radicals in estrogen induction of HCC by measuring detoxifying enzyme activities and levels of 8-hydroxydeoxyguanosine (8-OH-dG) and by assessing the effects of concomitant vitamin C, vitamin E or beta-carotene administration on hepatocarcinogenesis. During 12 months oral administration of EE (0.075 or 0.75 mg/day), the 8-OH-dG levels reached peak values after 1 month, when they were significantly elevated as compared with the controls. Glutathione peroxidase demonstrated a tendency to decrease. Histologically, pre-neoplastic lesions assessed by immunohistochemical staining for placental glutathione S-transferase (GST-P) were first observed at 2 months in the groups given 0.075 and 0.75 mg/day of EE alone, with incidences of HCC at 12 months being 8.7% and 38.5% respectively. Combined administration of vitamins with 0.075 mg EE/day reduced the elevation of the 8-OH-dG levels. GST-P-positive lesions were first observed at 4 months in the vitamin E group and at 6 months in the vitamin C and beta-carotene groups. As compared with the value in the 0.075 mg EE alone group, vitamin administration significantly reduced the numbers of GST-P-positive foci after 12 months of treatment. The incidences of HCC at 12 months were 0% in the vitamin C group, 4.5% in the vitamin E group and 4.8% in the beta-carotene group, i.e. administration of the vitamins inhibited the development of GST-P-positive foci, with suppression of HCC. The results thus suggest that free radicals play an important role in the induction of HCC by estrogen.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Anticarcinogenic Agents; Ascorbic Acid; beta Carotene; Carotenoids; Deoxyguanosine; DNA Damage; Estradiol Congeners; Female; Free Radicals; Glutathione Peroxidase; Glutathione Transferase; Immunohistochemistry; Liver; Liver Neoplasms, Experimental; Precancerous Conditions; Rats; Rats, Wistar; Reactive Oxygen Species; Vitamin E

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

Effects of a lipophilic derivative of vitamin C, 2-O-octadecylascorbic acid (CV-3611), as well as its parent L-ascorbic acid (AscA), DL-alpha-tocopherol (alpha-T) and its hydrophilic derivative, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), on the number and size of gamma-glutamyltransferase (GGT)-positive putative preneoplastic lesions were examined and compared with their influences on 8-hydroxyguanine formation in DNA and 2-thiobarbituric acid-reacting substance generation in the livers of rats fed a choline-deficient, L-amino acid-defined (CDAA) diet for 12 weeks. A total of 90 male Fischer 344 rats, 6 weeks old, were divided into 18 groups each consisting of five rats. Group 1 received the CDAA diet alone; Groups 2, 3 and 4 received the CDAA diet containing respectively 0.01, 0.05 and 0.10% CV-3611; Groups 5-7, 8-10 and 11-13 similarly received the CDAA diet containing AscA, alpha-T and Trolox, respectively, at these same low, middle and high concentrations; Group 14 received a choline-supplemented, L-amino acid-defined (CSAA) diet alone; Groups 15-18 were given the CSAA diet containing CV-3611, AscA, alpha-T and Trolox, respectively, all at the 0.10% level. While all four vitamin derivatives exerted inhibitory effects on all four parameters, in each case dose-dependently, CV-3611 demonstrated the most pronounced effects. The present results indicated that lipophilic vitamin C derivatives may be particularly effective chemopreventive agents against CDAA diet-associated, oxidative stress-related hepatocarcinogenesis via its superior antioxidative properties.

Topics: Amino Acids; Animals; Ascorbic Acid; Choline Deficiency; Diet; DNA; Enzyme Induction; Free Radical Scavengers; gamma-Glutamyltransferase; Liver Neoplasms, Experimental; Male; Precancerous Conditions; Rats; Rats, Inbred F344; Thiobarbituric Acid Reactive Substances; Vitamin E

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

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

A total of 391 gastric juice samples was collected from Ji Yuan and An Shi counties, high and medium risk areas of esophageal carcinoma in Henan province. NDMA, NDEA, NMBzA, NPip and unknown compounds were assayed in the fasting gastric juice. Among these nitrosamines, NMBzA, NPyr and NPip were specific in inducing esophageal cancer in animals. The amount of nitrosamines in the gastric juice collected from Ji Yuan county was higher than that from An Shi county. The exposure level of nitrosamines of subjects from these two localities were significantly different (P < 0.001). There was a positive relationship between the nitrosamines exposure level and esophageal cancer mortality rate. The amount of gastric N-nitrosamines from An Shi subjects as treated with vitamin C was reduced. It is evident that vitamin C can inhibit N-nitrosamine formation in the stomach, thereby, reducing the N-nitrosamines exposure level.

Topics: Adult; Aged; Ascorbic Acid; Dimethylnitrosamine; Esophageal Neoplasms; Esophagus; Female; Gastric Juice; Humans; Hyperplasia; Male; Middle Aged; N-Nitrosopyrrolidine; Nitrosamines; Precancerous Conditions

Five non-genotoxic chemicals previously demonstrated to be bladder cancer promoters in 36-week in vivo assays for carcinogenesis were reevaluated in a 20-week experiment in order to assess the summation influence of dietary uracil, a component of RNA, on the development of (pre)neoplastic lesions. The test chemicals, sodium bicarbonate, sodium L-ascorbate, sodium citrate, butylated hydroxytoluene and ethoxyquin, were mixed into the diet at concentrations of 3%, 5%, 5%, 1% and 0.8%, respectively, and administered to male F344 rats after initiation with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks. The test chemicals were given from the 4th to the 8th and the 11th to 20th experimental weeks, uracil being administered at the level of 3% in the diet during the intervening period. Rats in the control group received only BBN and uracil. All animals were killed at week 20 and the bladders were evaluated for the occurrence of putative preneoplastic papillary or nodular (PN) hyperplasia and tumors. Significant increase in the occurrence of PN hyperplasia was observed in all groups initiated with BBN and fed uracil and test chemicals. Quantitative values for papillomas were also significantly increased except in the ethoxyquin-treated group. The results confirm that uracil given in the middle of the post-initiation stage enhances the promoting activity of chemicals and suggest that the use of this chemical might be useful to reduce the duration of current bioassays for bladder chemical carcinogens.

Topics: Animals; Ascorbic Acid; Body Weight; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Butylhydroxybutylnitrosamine; Carcinogens; Epithelium; Ethoxyquin; Male; Mucous Membrane; Organ Size; Papilloma; Precancerous Conditions; Rats; Rats, Inbred F344; Uracil; Urinary Bladder; Urinary Bladder Neoplasms

A study was made on the effects of long-term dietary administration of beta-carotene, vitamin C, vitamin E and selenium, either alone or in combination, on azaserine-induced pancreatic carcinogenesis in rats. Male Wistar rats were given two i.p. injections of 30 mg azaserine per kg body weight at 19 and 26 days of age. The rats were allocated to eight groups of 40 animals each and were fed an AIN-76 diet rich in saturated fat (20% lard), either as such or after supplementation with beta-carotene, vitamin C, beta-carotene + vitamin C, vitamin E, selenium, vitamin E + selenium, or the combination of all micronutrients investigated. Fifteen months after the last treatment with azaserine the survivors were killed. The pancreata were examined for the number and size of advanced putative preneoplastic lesions and the number of neoplasms as well. Rats maintained on a diet high in either beta-carotene, vitamin C or selenium developed significantly less atypical acinar cells nodules, adenomas and carcinomas as compared to controls. The number of tumour-bearing animals was significantly lower in the groups fed the diet high in beta-carotene or selenium. In animals of the group given a diet high in all micronutrients investigated, both the number and incidence of pancreatic tumours was lower than in all other groups. It was concluded that selenium, beta-carotene and vitamin C, alone as well as in combination, have an inhibitory effect on pancreatic carcinogenesis induced in rats by azaserine.

Topics: Animals; Ascorbic Acid; Azaserine; beta Carotene; Body Weight; Carotenoids; Diet; Drug Combinations; Liver; Male; Organ Size; Pancreas; Pancreatic Neoplasms; Precancerous Conditions; Rats; Rats, Inbred Strains; Regression Analysis; Selenium; 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

Since both sodium L-ascorbate (Na-AsA) and sodium saccharin (Na-Sac) promote two-stage bladder carcinogenesis in rats, synergism of the two chemicals was investigated with special reference to the role of urinary pH and Na+ concentration. Male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in the drinking water for 4 wk and then treated with basal diet containing 5% Na-Sac, 5% Na-AsA, 5% Na-Sac plus 5% Na-AsA, 5% L-ascorbic acid (AsA), 5% Na-Sac plus 5% AsA, or no added chemical for 32 wk. Treatment with Na-Sac or Na-AsA alone significantly increased the induction of neoplastic and preneoplastic lesions of the bladder. Na-Sac plus Na-AsA also induced these bladder lesions significantly when compared with the controls, and the number of lesions was greater than the sum of the lesions in the groups treated with Na-Sac alone or Na-AsA alone. In contrast, the induction of carcinomas and papillomas in rats treated with Na-Sac plus AsA was not significantly different from the controls. In addition Na-Sac plus Na-AsA produced an elevation of urinary pH and Na+ concentrations, although the increases were not different from those in rats fed Na-Sac or Na-AsA alone. Na-Sac plus AsA, however, did not cause elevation of urinary pH, although it increased urinary Na+ concentration. Thus, the bladder carcinogenesis promotion by Na-Sac was synergized by Na-AsA and inhibited by AsA. This modulation was associated with changes of urinary pH and Na+ concentration.

Topics: Animals; Ascorbic Acid; Drug Synergism; Male; Precancerous Conditions; Rats; Rats, Inbred F344; Saccharin; Sodium; Urinary Bladder Neoplasms

Both plasma and dietary measures of vitamin A status were investigated along with previously established risk factors (number of sexual partners, age at first intercourse, smoking, and oral contraceptive use) in a study of 117 in situ cervical cancer patients and 196 matched community controls in Sydney, Australia. Neither total calories nor retinol from foods was related to cancer risk, nor was plasma retinol. When plasma and dietary indexes were considered together, vitamin C, fruit juices, and plasma beta-carotene showed protective effects. Plasma beta-carotene reduced risk from top to bottom quartile by 80%, vitamin C by 60%, and fruit juices by 50%. Thus the evidence suggests that cancer risk is associated with some aspect of diet that is reflected in the effect of plasma beta-carotene. There is no clear effect of any one nutrient but fruit juices appear protective. Thus vitamin C and beta-carotene are likely candidates.

Topics: Adult; Aged; Ascorbic Acid; Australia; beta Carotene; Carcinoma in Situ; Carotenoids; Diet; Female; Humans; Middle Aged; Precancerous Conditions; Uterine Cervical Neoplasms; Vitamin A

The effects of vitamins A, C and E on the development of putative preneoplastic foci in exocrine pancreas were investigated in azaserine-treated rats and N-nitrosobis(2-oxoproypy)amine-treated hamsters. The animals were fed a semipurified diet high in saturated fat (20% lard) either or not supplemented with vitamin A, vitamin C or vitamin E. A separate group maintained on a diet low in saturated fat (5% lard) was incorporated as extra controls. The animals were given their diets 12 days after the last treatment with carcinogen. At 4 months postinitiation, the pancreata were quantitatively examined for both the number and size of early, putative preneoplastic lesions and the presence of neoplastic lesions. Rats as well as hamsters maintained on 5% lard exhibited a significantly lower number of putative preneoplastic pancreatic lesions than animals fed a diet containing 20% lard. Growth of acidophilic but not of basophilic foci was inhibited in rats of the high vitamin A and C group, whereas vitamin E exerted an inhibitory effect on growth of basophilic but not of acidophilic foci. In hamsters maintained on a diet high in vitamins A or C, the number of early ductular lesions was significantly decreased, whereas the number of (micro)carcinomas was increased. Vitamin E did not have any modulating effect on development of ductal lesions in hamster pancreas.

Topics: Animals; Ascorbic Acid; Cricetinae; Dietary Fats; Energy Metabolism; Male; Mesocricetus; Pancreas; Pancreatic Neoplasms; Precancerous Conditions; Rats; Rats, Inbred Strains; Vitamin A; Vitamin E

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

Topics: Ascorbic Acid; Dose-Response Relationship, Drug; Esophageal Neoplasms; Gastrointestinal Neoplasms; Humans; Kinetics; Nitrosamines; Nitroso Compounds; Precancerous Conditions; Proline; Risk; Thiazoles; Thiazolidines

Traditional methods for prevention of large bowel cancer rely on surveillance of patients with known precursors of bowel cancer, namely ulcerative colitis and those genetically linked polyposis syndromes that have malignant potential. Identification of heritable bowel cancer families and solitary polyp--cancer families provide additional populations that merit intensive scrutiny. Persuasive, if circumstantial, evidence suggests that maintaining patients free of large bowel polyps reduces the risk of developing large bowel cancer. Prospects for prevention of large bowel cancer are extended by recognition that a diet low in fat may reduce the risk of large bowel cancer. Furthermore, there is considerable evidence in animals that a variety of antioxidants limit large bowel carcinogenesis and preliminary evidence in man that these agents may control large bowel neoplasia.

Topics: Adenoma; Ascorbic Acid; Colitis, Ulcerative; Colonic Neoplasms; Diet; Humans; Polyps; Precancerous Conditions

L-ascorbic acid has been shown to reduce the elevated level of urinary chemiluminescence found in patients with bladder cancer. Thus, it has been suggested that vitamin C might be efficacious in bladder tumor prophylaxis. However, there is no clinical evidence to support this thesis. We evaluated whether L-ascorbic acid given concomitantly with the urinary carcinogen FANFT was capable of reducing the incidence of subsequent bladder tumors. No inhibitory effect was observed. Unless evidence is obtained demonstrating bladder tumor prevention by L-ascorbic acid its routine administration to patients with bladder cancer is not indicated.

Topics: Animals; Ascorbic Acid; Carcinogens; Carcinoma, Transitional Cell; Drug Evaluation; Formamides; Metaplasia; Mice; Mice, Inbred C3H; Nitrofurans; Precancerous Conditions; Thiazoles; Urinary Bladder; Urinary Bladder Neoplasms

Topics: Animals; Ascorbic Acid; Chemical and Drug Induced Liver Injury; Female; Guinea Pigs; Liver; Liver Neoplasms; Lung; Male; Morpholines; Nitrates; Nitroso Compounds; Precancerous Conditions

Topics: Animals; Ascorbic Acid; Carcinogens; Carcinoma, Squamous Cell; Humans; Mice; Neoplasms, Experimental; ortho-Aminobenzoates; Oxidation-Reduction; Precancerous Conditions; Urinary Bladder Neoplasms

Topics: Aged; Anemia, Sideroblastic; Ascorbic Acid; Autopsy; Blood Cell Count; Blood Transfusion; Bone Marrow; Bone Marrow Cells; Bone Marrow Examination; Erythrocytes; Erythropoiesis; Folic Acid; Follow-Up Studies; Humans; Hyperplasia; Iron; Leukemia, Myeloid; Male; Middle Aged; Monocytes; Muramidase; Precancerous Conditions; Pyridoxine; Vitamin B 12