ascorbic-acid and Lung-Neoplasms

Vitamin C is used in modern medicine supplements for treatment of various disorders associated with oxidative stress, inflammation and immune dysregulation. In this review article, experimental and clinical results regarding the effects of vitamin C on respiratory immunologic, and allergic diseases are reviewed. Various databases and appropriate keywords are used to search the effect of vitamin C on respiratory diseases until the end of May 2022. Books, theses and articles were included. These studies assessed the effects of vitamin C on respiratory disorders including asthma, chronic obstructive pulmonary disease (COPD), lung infection and lung cancer. Vitamin C showed relaxant effect on tracheal smooth muscle via various mechanisms. The preventive effects of vitamin C were mediated by antioxidant, immunomodulatory and anti-inflammatory mechanisms in the experimental animal models of different respiratory diseases. Some clinical studies also indicated the effect of vitamin C on lung cancer and lung infections. Therefore, vitamin C could be used a preventive and/or relieving therapy in respiratory diseases.

Topics: Animals; Ascorbic Acid; Asthma; Lung Neoplasms; Pneumonia; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Vitamins

The purpose of this study was to summarize the evidence from epidemiological studies concerning associations between diet and the effectiveness of treatment for lung cancer. For this review, a literature search has been conducted in the EMBASE and PubMed databases, including papers published between 1977 and June 2022. The term "lung cancer" was used in conjunction with "diet". Footnotes from the selected papers were also analyzed. The present study is in line with the recommendations included in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The review included studies involving adults, including randomized controlled trials (RCTs) and cohort and observational studies. In total, 863 papers were found, with duplicates excluded. Ultimately, 20 papers were reviewed. The present systematic review indicates that vitamin A, ascorbic acid (vitamin C), vitamin E, selenium, and zinc-as antioxidants-can strengthen the body's antioxidant barrier. Furthermore, preoperative immunonutrition may not only improve perioperative nutritional status following induction chemoradiotherapy in lung cancer surgery patients but also reduce the severity of postoperative complications. Similarly, a protein supply may exert a beneficial effect on human health by increasing average body weight and muscle mass. Omega-3 fatty acid content in the diet and the consumption of their main source, fish, may have some regulatory effect on inflammation in patients with lung cancer treated with chemotherapy and radiotherapy. In addition,

Topics: Adult; Animals; Antioxidants; Ascorbic Acid; Diet; Fatty Acids, Omega-3; Humans; Lung; Lung Neoplasms; Vitamins

This is the second update of this Cochrane Review. Some studies have suggested a protective effect of antioxidant nutrients and higher dietary levels of fruits and vegetables on lung cancer.. To determine whether vitamins and minerals and other potential agents, alone or in combination, reduce lung cancer incidence and lung cancer mortality in healthy populations.. We searched CENTRAL, MEDLINE and Embase from 1974 to May 2019 and screened references included in published studies and reviews.. We included randomised controlled trials (RCTs) comparing vitamins or mineral supplements with placebo, administered to healthy people with the aim of preventing lung cancer.. Four review authors independently selected the trials to be included in the review, assessed their methodological quality and extracted data. For dichotomous outcomes we calculated risk ratios (RRs) and 95% confidence intervals (CIs) and pooled results using the random-effects model. We assessed the risk of bias using Cochrane's 'Risk of bias' assessment tool and certainty of evidence using the GRADE approach.. In this update, we identified three new trials for a total of 12 studies. Six analysed vitamin A, three vitamin C, three combined vitamin D3 + calcium, four vitamin E combined with other products, one selenium supplements and nine studied combinations of two or more products. Four studies included only men and five only women. Vitamin A results in little to no difference in lung cancer incidence (RR 1.09, 95% CI 1.00 to 1.19; 5 RCTs, 212314 participants; high-certainty evidence) and lung cancer mortality (RR 1.06, 95% CI 0.81 to 1.38; 3 RCTs, 190118 participants; high-certainty evidence). But in smokers or asbestos workers vitamin A increases the risk of lung cancer incidence (RR 1.10, 95% CI 1.01 to 1.20; 3 RCTs, 43995 participants; high-certainty evidence), lung cancer mortality (RR 1.18, 95% CI 1.01 to 1.38; 2 RCTs, 29426 participants; high-certainty evidence) and all-cause mortality (RR 1.09, 95% CI 1.05 to 1.13; 2 RCTs, 32883 participants; high-certainty evidence). Vitamin A increases the risk of minor side effects, such as yellowing of the skin and minor gastrointestinal symptoms (high-certainty evidence). Vitamin C likely results in little to no difference in lung cancer incidence (RR 1.29, 95% CI 0.67 to 2.49; 2 RCTs, 14953 participants; moderate-certainty evidence). In women, vitamin C increases the risk of lung cancer incidence (RR 1.84, 95% CI 1.14 to 2.95; 1 RCT, 7627 participants; high-certainty evidence). In men, vitamin C results in little to no difference in mortality for lung cancer (RR 0.81, 95% CI 0.53 to 1.23; 1 RCT, 7326 participants; high-certainty evidence). Vitamin D + calcium may result in little to no difference in lung cancer incidence in postmenopausal women (RR 0.90, 95% CI 0.39 to 2.08; 3 RCTs, 37601 women; low-certainty evidence). Vitamin E results in little to no difference in lung cancer incidence (RR 1.01, 95% CI 0.90 to 1.14; 3 RCTs, 36841 participants; high-certainty evidence) or to lung cancer mortality (RR 0.96, 95% CI 0.77 to 1.18; 2 RCTs, 29214 participants; high-certainty evidence), but increases the risk of haemorrhagic strokes (hazard ratio (HR), 1.74, 95% CI 1.04 to 2.91; 1 RCT, 14641 participants; high-certainty evidence). Calcium results in little to no difference in lung cancer incidence in postmenopausal women (RR 0.65, 95% CI 0.13 to 3.18; 1 RCT, 733 participants) or in risk of renal calculi (RR 1.94, 95% CI 0.20 to 18.57; 1 RCT, 733 participants; low-certainty evidence). Selenium in men results in little t. Well-designed RCTs have shown no beneficial effect of supplements for the prevention of lung cancer and lung cancer mortality in healthy people. Vitamin A supplements increase lung cancer incidence and mortality in smokers or persons exposed to asbestos. Vitamin C increases lung cancer incidence in women. Vitamin E increases the risk of haemorrhagic strokes.

Topics: alpha-Tocopherol; Ascorbic Acid; beta Carotene; Calcium, Dietary; Cholecalciferol; Confidence Intervals; Dietary Supplements; Female; Health Status; Humans; Incidence; Lung Neoplasms; Male; Minerals; Randomized Controlled Trials as Topic; Selenium; Selenium Compounds; Sex Factors; Vitamin A; Vitamin E; Vitamins

Epidemiological studies evaluating the association between the intake of vitamin C and lung cancer risk have produced inconsistent results. We conducted a meta-analysis to assess the association between them. Pertinent studies were identified by a search of PubMed, Web of Knowledge and Wan Fang Med Online through December of 2013. Random-effect model was used to combine the data for analysis. Publication bias was estimated using Begg's funnel plot and Egger's regression asymmetry test. Eighteen articles reporting 21 studies involving 8938 lung cancer cases were included in this meta-analysis. Pooled results suggested that highest vitamin C intake level versus lowest level was significantly associated with the risk of lung cancer [summary relative risk (RR) = 0.829, 95%CI = 0.734-0.937, I(2) = 57.8%], especially in the United States and in prospective studies. A linear dose-response relationship was found, with the risk of lung cancer decreasing by 7% for every 100 mg/day increase in the intake of vitamin C [summary RR = 0.93, 95%CI = 0.88-0.98]. No publication bias was found. Our analysis suggested that the higher intake of vitamin C might have a protective effect against lung cancer, especially in the United States, although this conclusion needs to be confirmed.

Topics: Ascorbic Acid; Dietary Supplements; Humans; Lung Neoplasms; Odds Ratio; Publication Bias; Risk

Manufacturers have developed prototype cigarettes yielding reduced levels of some tobacco smoke toxicants, when tested using laboratory machine smoking under standardised conditions. For the scientific assessment of modified risk tobacco products, tests that offer objective, reproducible data, which can be obtained in a much shorter time than the requirements of conventional epidemiology are needed. In this review, we consider whether biomarkers of biological effect related to oxidative stress can be used in this role. Based on published data, urinary 8-oxo-7,8-dihydro-2-deoxyguanosine, thymidine glycol, F2-isoprostanes, serum dehydroascorbic acid to ascorbic acid ratio and carotenoid concentrations show promise, while 4-hydroxynonenal requires further qualification.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Ascorbic Acid; Biomarkers; Carotenoids; Dehydroascorbic Acid; Deoxyguanosine; F2-Isoprostanes; Humans; Lung Neoplasms; Oxidative Stress; Risk; Smoking; Thymidine; Tobacco Products; Tobacco Smoke Pollution

This is an updated version of the original review published in Issue 2, 2003. Some studies have suggested a protective effect of antioxidant nutrients on lung cancer. Observational epidemiological studies suggest an association between higher dietary levels of fruits and vegetables containing beta-carotene and a lower risk of lung cancer.. To determine whether vitamins, minerals and other potential agents, alone or in combination, reduce incidence and mortality from lung cancer in healthy people.. For this update we have used a search strategy adapted from the design in the original review. The following electronic databases have been searched up to December 2011: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL). References included in published studies and reviews were also screened.. Included studies were randomised controlled clinical trials comparing different vitamins, mineral supplements or supplements with placebo, administered to healthy people with the aim of preventing lung cancer.. Two authors independently selected the trials to be included in the review, assessed the methodological quality of each trial and extracted data using a standardised form. For each study, relative risk and 95% confidence limits were calculated for dichotomous outcomes and pooled results were calculated using the random-effect model.. In the first version of this review four studies were included; in this review update, an additional five studies have been included. Four studies included only males and two only females; two studies included only participants considered at high risk, namely smokers or exposed to asbestos, and one study included people deficient in many micronutrients. Six studies analysed vitamin A, three vitamin C, four vitamin E, one selenium supplements, and six studied combinations of two or more products. All the RCTs included in this review were classified as being of low risk of bias.For people not at high risk of lung cancer and compared to placebo, none of the supplements of vitamins or minerals or their combinations resulted in a statistically significant difference in lung cancer incidence or mortality, except for a single study that included 7627 women and found a higher risk of lung cancer incidence for those taking vitamin C but not for total cancer incidence, but that effect was not seen in males or when the results for males and females were pooled.For people at high risk of lung cancer, such as smokers and those exposed to asbestos and compared to placebo, beta-carotene intake showed a small but statistically significant higher risk of lung cancer incidence, lung cancer mortality and for all-causes mortality.. There is no evidence for recommending supplements of vitamins A, C, E, selenium, either alone or in different combinations, for the prevention of lung cancer and lung cancer mortality in healthy people. There is some evidence that the use of beta-carotene supplements could be associated with a small increase in lung cancer incidence and mortality in smokers or persons exposed to asbestos.

Topics: alpha-Tocopherol; Ascorbic Acid; beta Carotene; Dietary Supplements; Female; Health Status; Humans; Lung Neoplasms; Male; Minerals; Randomized Controlled Trials as Topic; Selenium Compounds; Vitamin A; Vitamins

Intakes of vitamins A, C and E and folate have been hypothesized to reduce lung cancer risk. We examined these associations in a pooled analysis of the primary data from 8 prospective studies from North America and Europe. Baseline vitamin intake was assessed using a validated food-frequency questionnaire, in each study. We calculated study-specific associations and pooled them using a random-effects model. During follow-up of 430,281 persons over a maximum of 6-16 years in the studies, 3,206 incident lung cancer cases were documented. Vitamin intakes were inversely associated with lung cancer risk in age-adjusted analyses; the associations were greatly attenuated after adjusting for smoking and other risk factors for lung cancer. The pooled multivariate relative risks, comparing the highest vs. lowest quintile of intake from food-only, were 0.96 (95% confidence interval (CI) 0.83-1.11) for vitamin A, 0.80 (95% CI 0.71-0.91) for vitamin C, 0.86 (95% CI 0.76-0.99) for vitamin E and 0.88 (95% CI 0.74-1.04) for folate. The association with vitamin C was not independent of our previously reported inverse association with beta-cryptoxanthin. Further, vitamin intakes from foods plus supplements were not associated with a reduced risk of lung cancer in multivariate analyses, and use of multivitamins and specific vitamin supplements was not significantly associated with lung cancer risk. The results generally did not differ across studies or by sex, smoking habits and lung cancer cell type. In conclusion, these data do not support the hypothesis that intakes of vitamins A, C and E and folate reduce lung cancer risk.

Topics: Antioxidants; Ascorbic Acid; Diet; Dietary Supplements; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Multivariate Analysis; Prospective Studies; Risk Factors; Vitamin A; Vitamin E

Tobacco use is the leading risk factor for lung cancer, yet in addition to smoking habit, diet may also play a role in the disease's appearance. While there are reports to indicate that antioxidant vitamins and carotenoids may decrease the risk of lung cancer, results to date have been somewhat ambiguous. This review aimed to describe the results yielded by different studies, which have addressed antioxidant vitamin intake and lung cancer, and to indicate the mechanisms whereby these nutrients might be exercising their activity. Antioxidant vitamins were observed to have no clear protective effect, though there was some evidence pointing to a protective role for vitamins C and E. Vitamin A, in contrast, evinced no clear effect. Insofar as provitamin A carotenoids were concerned, lutein/zeaxanthin, lycopene and alpha-carotene displayed a certain protective trend, yet beta-carotene exhibited no protective effect whatsoever; and indeed, there was speculation as to whether it might even be pernicious in smokers. Beta-criptoxanthin, on the other hand, showed a more consistent protective effect. The study highlighted the need to conduct further research on smokers and non-smokers alike, and in particular, to investigate the effect, if any, on lung cancer of carotenoids or vitamins when ingested in differing dosages.

Topics: Animals; Antioxidants; Ascorbic Acid; Carotenoids; Cohort Studies; Humans; Lung Neoplasms; Smoking; Vitamin A; Vitamin E; Vitamins

Nickel compounds are known to cause respiratory cancer in humans and induce tumors in experimental animals. The underlying molecular mechanisms may involve genotoxic effects; however, the data from different research groups are not easy to reconcile. Here, we challenge the common premise that direct genotoxic effects are central to nickel carcinogenesis and probably to that of other metals. Instead, we propose that it is formation of metal complexes with proteins and other molecules that changes cellular homeostasis and provides conditions for selection of cells with transformed phenotype. This is concordant with the major requirement for nickel carcinogenicity, which is prolonged action on the target tissue. If DNA is not the main nickel target, is there another unique molecule that can be attacked with carcinogenic consequences? Our recent observations indicate that ascorbate may be such a molecule. Nickel depletes intracellular ascorbate, which leads to the inhibition of cellular hydroxylases, manifested by the loss of hypoxia-inducible factor (HIF)-1alpha and -2alpha hydroxylation and hypoxia-like stress. Proline hydroxylation is crucial for collagen and extracellular matrix assembly as well as for assembly of other protein molecules that have collagen-like domains, including surfactants and complement. Thus, the depletion of ascorbate by chronic exposure to nickel could be deleterious for lung cells and may lead to lung cancer. Key words: ascorbate, carcinogenesis, collagens, extracellular matrix, hypoxia-inducible transcription factor, metals, nickel, protein hydroxylation.

Topics: Animals; Antioxidants; Ascorbic Acid; Cell Transformation, Neoplastic; DNA Damage; Homeostasis; Humans; Hydroxylation; Lung Neoplasms; Nickel; Proline; Protein Binding; Rats

Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.. To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.. We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.. We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.. Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.. Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis

Topics: Ascorbic Acid; Avitaminosis; Blood Coagulation; Breast Neoplasms; Carotenoids; Chronic Disease; Colorectal Neoplasms; Coronary Disease; Dietary Supplements; Female; Folic Acid; Fractures, Bone; Humans; Lung Neoplasms; Male; Neoplasms; Neural Tube Defects; Prostatic Neoplasms; Risk Factors; Vitamin A; Vitamin B 12; Vitamin B 6; Vitamin D; Vitamin E; Vitamin K; Vitamins

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Cell Transformation, Neoplastic; Diet; Free Radicals; Guinea Pigs; Humans; Incidence; Lung Neoplasms; Melanoma; Mice; Mice, Hairless; Models, Chemical; Neoplasms; Neoplasms, Radiation-Induced; Oxygen; Partial Pressure; Prospective Studies; Reactive Oxygen Species; Retrospective Studies; Selenium; Singlet Oxygen; Skin Neoplasms; Smoking; Structure-Activity Relationship; Ultraviolet Rays; Vegetables; Vitamin E

Lung cancer is one of major public health problems facing the world today, owing to the high incidence of the disease and its poor prognosis. Although the principal cause of lung cancer is tobacco use, smokers find it extremely difficult to quit the habit. Hence, there is a need to take action targeted at other risk factors for this disease. One such factor is diet, which is known to be able to raise or lower the risk of lung cancer. This paper seeks to complement other reviews in the field and to shed more light both on the influence that dietary factors may have upon the occurrence of this neoplasm and on the causes of this possible effect.

Topics: Ascorbic Acid; Carotenoids; Diet; Fruit; Humans; Lung Neoplasms; Phytotherapy; Risk Factors; Vegetables

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Cell Division; Dietary Supplements; DNA Damage; Dose-Response Relationship, Drug; Humans; Lung Neoplasms; Oxidation-Reduction; Risk Factors; Smoking; Vitamin E

Lung cancer is the most common cancer in the world, and smoking is the major risk factor, accounting for about 90% of the cases. Diet has also been implicated in the development of lung cancer, although the specific nutrients remain to be elucidated. Vitamins with antioxidant activity have received much attention. beta-Carotene, the most efficient provitamin A, was found to be inversely related to the risk of lung cancer in many prospective epidemiological studies, especially in studies measuring serum concentrations of beta-carotene. The findings from controlled trials, however, contradict the hypothesis that beta-carotene could prevent lung cancer, but rather suggest increased risk of lung cancer with supplementary beta-carotene. Data from both prospective studies and a controlled trial suggest no role for vitamin E in lung carcinogenesis. Some prospective epidemiological studies suggest an inverse relationship between dietary vitamin C and the risk of lung cancer, but due to the high correlation between dietary vitamin C and vegetable and fruit intake the independent role of dietary vitamin C is difficult to estimate. Studies using prediagnostic plasma concentrations of ascorbic acid do not support the involvement of vitamin C in lung carcinogenesis, and no controlled trials of vitamin C on lung cancer have been published. Thus, supplementation with antioxidant vitamins cannot be recommended for the prevention of lung cancer. Non-smoking is the most important target in the prevention of lung cancer. High intakes of vegetables and fruits may provide additional protection and are unlikely to be harmful.

Topics: Ascorbic Acid; beta Carotene; Humans; Lung Neoplasms; Risk Factors; Vitamin A; Vitamins

A critical review of epidemiological studies on diet and lung cancer over the last 20+ years has not provided overwhelming evidence that higher consumption of vegetables, fruit, low-fat/low-cholesterol foods or such micronutrients as carotenoids, selenium and vitamins A, C or E is associated with reduced lung cancer risk. Results from case-control studies have been more positive, with about one half showing fruit and vegetables or their associated micronutrients to be associated with reduced risk. However, most results from cohort and serum micronutrient studies, which avoid the problems of inaccurate accounting of diet and recall bias, were statistically insignificant. Moreover, although most studies were conducted on white male smokers in North America and Europe, the few studies which found significant contrary trends were among subjects of different backgrounds, i.e., black American males and Chinese women in China. Since male smokers vs. nonsmokers in Europe, North America and Japan have been shown in other studies to be lower consumers of fruit/vegetables, and less likely to pursue "perceived healthier lifestyles," the possibility that some of the epidemiological findings on diet and lung cancer are artifactually due to inadequate adjustment for behavioral correlates of smoking and health seekers in a particular society must be considered. This is especially true with recent chemoprevention trials showing higher lung cancer incidence and deaths among consumers of beta-carotene supplements vs. placebo.

Topics: Ascorbic Acid; beta Carotene; Case-Control Studies; Diet; Dietary Fats; Fruit; Humans; Life Style; Lung Neoplasms; Odds Ratio; Risk; Smoking; Vegetables; Vitamin A

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

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

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

Topics: Ascorbic Acid; Carcinogens, Environmental; Diet; Humans; Lung Neoplasms; Mutagens; Nutritional Physiological Phenomena; Selenium; Smoking; Vitamin A; Vitamin E

We reviewed the human epidemiologic studies of the possible protective effect against lung cancer of various dietary constituents, including preformed vitamin A, carotene, vitamin E, selenium, and vitamin C. Beta carotene has strong potential as a protective agent, though constituents of green and yellow vegetables other than carotene may account for the reduced cancer incidence observed in many studies. Selenium also deserves attention as a potential chemopreventive nutrient, though data are limited. Data on vitamin E are sparse and inconclusive, and there is little evidence that vitamin C provides protection against human lung cancer. It is likely that cessation of cigarette smoking would have a far greater influence on reducing lung cancer incidence than any known dietary modification.

Topics: Ascorbic Acid; Diet; Humans; Lung Neoplasms; Selenium; Vitamin A; Vitamin E

Topics: Adenoma; Amines; Aminopyrine; Animals; Ascorbic Acid; Dimethylnitrosamine; Female; Liver; Lung Neoplasms; Mice; Morpholines; Neoplasms, Experimental; Nitrites; Nitrosamines; Nitroso Compounds; Pregnancy; Rats; Urea

Topics: Administration, Oral; Aged; Antigen-Antibody Reactions; Ascorbic Acid; Aspirin; Child; Common Cold; Female; Fenfluramine; Humans; Hypersensitivity; Leukemia; Leukocytes; Lung Neoplasms; Male; Mouth Mucosa; Nutritional Requirements; Scurvy

Pharmacological ascorbate has been proposed as a potential anti-cancer agent when combined with radiation and chemotherapy. The anti-cancer effects of ascorbate are hypothesized to involve the autoxidation of ascorbate leading to increased steady-state levels of H

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Chemoradiotherapy; Female; Glioblastoma; Humans; Hydrogen Peroxide; Iron; Lung Neoplasms; Male; Mice, Nude; Oxygen; Radiation-Sensitizing Agents; Xenograft Model Antitumor Assays

Ascorbic acid (AA) infusion and modulated electrohyperthermia (mEHT) are widely used by integrative cancer practitioners for many years. However, there are no safety and pharmacokinetics data in Chinese cancer patients. We carried out a clinical trial to evaluate the safety and pharmacokinetics of those methods in patients with stage III-IV non-small cell lung cancer (NSCLC). Blood ascorbic acid in the fasting state was obtained from 35 NSCLC patients; selecting from them 15 patients with stage III-IV entered the phase I study. They were randomized allocated into 3 groups, and received doses 1.0, 1.2, 1.5g/kg AA infusions. Participants in the first group received intravenous AA (IVAA) when mEHT was finished, in the second group IVAA was administered simultaneously with mEHT and in the third group IVAA was applied first, and followed with mEHT. Pharmacokinetic profiles were obtained when they received solely IVAA and when IVAA in combination with mEHT. The process was applied 3 times a week (every other day, weekend days off) for 4weeks. We found that fasting plasma AA levels were significantly correlated with stage of the disease. Peak concentration of AA was significantly higher in the simultaneous treatments than in other combinations with mEHT or in solely IVAA-managed groups. IVAA synergy with simultaneous mEHT is safe and the concomitant application significantly increases the plasma AA level for NSCLC patients.

Topics: Administration, Intravenous; Aged; Ascorbic Acid; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Electric Stimulation Therapy; Female; Humans; Hyperthermia, Induced; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxalic Acid; Quality of Life; Single-Blind Method

One of the main after-effects of chemotherapy used in cancer treatment is an augmented production of reactive oxygen species (ROS). In turn ROS become a source of unwanted side effects of chemotherapy, often forcing the discontinuation of the therapy. Ascorbic acid (vitamin C), being an antioxidant, can strengthen the antioxidative barrier of an organism. The aim of the study was an assessment of the concentrations of A, C and E vitamins in the plasma of NSCLC patients undergoing chemotherapy supplemented with vitamin C.. 25 first-line chemotherapy patients with inoperable NSCLC, including 19 men and 6 women aged between 37-73 years (average age 60.1 +/- 8.8 years) have undergone the examination. Their chemotherapy has been supplemented with ascorbic acid (vitamin C dose of 600 mg per 24 hours). Control group consisted of 24 healthy individuals, including 18 men and 6 women aged between 49-71 years (average age 59.5 +/- 6.6 years). In cancer patients the concentration of A, C and E vitamins was assessed by spectrophotometry using T60V spectrophotometer (PG Instruments) before and after first-line chemotherapy which was supplemented with vitamin C. In control group the concentrations of antioxidative vitamins was assessed only once.. In comparison to the control group the concentrations of the A, C and E vitamins in the plasma of NSCLC patients was significantly lower (p < 0.05). After 6 weeks of chemotherapy supplemented with vitamin C a significant rise of concentrations (p < 0.05) of all the vitamins tested for was observed. The biggest rise was noted for vitamin C (99.8%).. The supplementation of the chemotherapy of NSCLC patients with C vitamin leads to rise of the low concentrations of A, C and E vitamins in the plasma. This suggests strengthening of the antioxidative barrier in patients.

Topics: Adult; Aged; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Carcinoma, Non-Small-Cell Lung; Dietary Supplements; Female; Food-Drug Interactions; Humans; Lung Neoplasms; Male; Middle Aged; Vitamin A; Vitamin E; Vitamins

Vitamin E and beta-carotene affect the immune function and might influence the predisposition of man to infections. To examine whether vitamin E or beta-carotene supplementation affects tuberculosis risk, we analysed data of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC)Study, a randomised controlled trial which examined the effects of vitamin E (50 mg/d) and beta-carotene (20 mg/d) on lung cancer. The trial was conducted in the general community in Finland in 1985-93; the intervention lasted for 6.1 years (median). The ATBC Study cohort consists of 29,023 males aged 50-69 years, smoking at baseline, with no tuberculosis diagnosis prior to randomisation. Vitamin E supplementation had no overall effect on the incidence of tuberculosis (risk ratio (RR) = 1.18; 95% CI 0.87, 1.59) nor had beta-carotene (RR = 1.07; 95% CI 0.80, 1.45). Nevertheless, dietary vitamin C intake significantly modified the vitamin E effect. Among participants who obtained 90 mg/d or more of vitamin Cin foods (n 13,502), vitamin E supplementation increased tuberculosis risk by 72 (95% CI 4, 185)%. This effect was restricted to participants who smoked heavily. Finally, in participants not supplemented with vitamin E, dietary vitamin C had a negative association with tuberculosis risk so that the adjusted risk was 60 (95% CI 16, 81)% lower in the highest intake quartile compared with the lowest. Our finding that vitamin E seemed to transiently increase the risk of tuberculosis in those who smoked heavily and had high dietary vitamin C intake should increase caution towards vitamin E supplementation for improving the immune system.

Topics: Aged; Antioxidants; Ascorbic Acid; beta Carotene; Diet; Dietary Supplements; Follow-Up Studies; Fruit; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Risk Assessment; Smoking; Tuberculosis; Vegetables; Vitamin E; Vitamins

In vitro and animal studies suggest that antitumor effect of chemotherapeutic agents may be enhanced by antioxidants. Therefore, we initiated a clinical study to test the efficacy of high-dose multiple antioxidants (vitamins C, E and beta carotene) as an adjunct to chemotherapy (paclitaxel and carboplatin) in non-small-cell lung cancer.. 136 patients of stage IIIb and stage IV NSCLC were randomized to receive chemotherapy (paclitaxel and carboplatin) alone (chemotherapy arm, n = 72) or chemotherapy in combination with ascorbic acid 6100 mg/day, dl-alpha-tocopherol (vitamin E) 1050 mg/day and beta-carotene 60 mg/day (combination arm, n = 64). Survival were calculated by the Kaplan-Meier method and compared using the log-rank test.. An overall response rate (RR) of 33% was observed in chemotherapy arm with 24 patients showing a partial response (PR) and none showing a complete response (CR). In combination arm the overall RR was 37% with 24 patients showing PR and two showing CR. The median survival times in chemotherapy arm and combination arm were nine and 11 months respectively. The overall survival (OS) rates in chemotherapy arm and combination arm at one year were 32.9% and 39.1%, and at two years, 11.1% and 15.6% respectively. None of these differences were statistically significant (p = 0.20). Toxicity profiles were similar in both arms.. These results do not support the concern that antioxidants might protect cancer cells from the free radical damage induced by chemotherapy. Larger trials are needed to demonstrate whether high-dose multiple antioxidants in conjunction with chemotherapy increase the response rates and/or survival time in advanced lung cancer.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Non-Small-Cell Lung; Drug Synergism; Female; Humans; Lung Neoplasms; Male; Middle Aged; Survival Analysis; Vitamin E

Despite the unexpected results from the beta-Carotene and Retinol Efficacy Trial (CARET) and similar supplementation trials showing that supplementation with beta-carotene increased, rather than decreased, lung cancer incidence, considerable interest remains in investigating how other compounds in fruits and vegetables may affect lung cancer risk. We used data from 14,120 CARET participants who completed food frequency questionnaires to examine associations of diet with lung cancer risk. After 12 years of follow-up (1989-2001), 742 participants developed lung cancer. We used Cox proportional hazards models to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs). Analyses were controlled for smoking, asbestos exposure, and other covariates. Analyses of specific botanical groups were also controlled for total fruit and vegetable intake. All models were stratified by CARET treatment arm, and all statistical tests were two-sided. Statistically significant associations of fruit and vegetable intake with lower lung cancer risk were restricted to the CARET placebo arm. The RR for highest versus lowest quintile of total fruit consumption in the placebo arm was 0.56 (95% CI, 0.39-0.81) with a two-sided P for trend = 0.003. Two specific botanical groups were associated with reduced risk of lung cancer. Compared with the lowest quintile of rosaceae fruit consumption, placebo participants in the top quintile had a RR of 0.63 (95% CI, 0.42-0.94; P for trend = 0.02); for cruciferae vegetables, the RR was 0.68 (95% CI, 0.45-1.04; P for trend = 0.01). We did not observe any statistically significant associations of fruit and vegetable intake with lung cancer risk among participants randomized to receive the CARET supplements (30 mg of beta-carotene and 25,000 IU of retinyl palmitate). This report provides evidence that plant foods have an important preventive influence in a population at high risk for lung cancer. However, persons who use beta-carotene supplements do not benefit from the protective compounds in plant foods.

Topics: Aged; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Small Cell; Double-Blind Method; Feeding Behavior; Female; Follow-Up Studies; Fruit; Humans; Lung Neoplasms; Male; Middle Aged; Placebos; Risk Factors; Statistics as Topic; Treatment Outcome; Vegetables; Vitamin A

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

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

Even though it is well established that oxygen-free radicals are the main mechanism responsible for the cytotoxicity produced during radiotherapy, the role of the human antioxidant defense system in clinical radiation oncology is still to be clarified. Changes in the human plasma total peroxyl radical trapping capacity (TRAP) and its individual components were followed during clinical radiotherapy for lung cancer. Sixteen patients receiving radical-aimed radiotherapy provided blood samples nine times during the treatment. Our hypothesis was that oxygen-free radical production increased by irradiation should decrease the plasma TRAP as a consequence of oxidative stress. Only a moderate reduction of the plasma TRAP was found during the therapy in the study group taken as a whole, but the development pattern of TRAP and its unidentified components were clearly different in those patients showing complete or partial response to the treatment and those in which the disease progressed unabated. Plasma ascorbate levels showed no significant changes during radiotherapy. A decrease in vitamin E concentrations was seen after 6 Gy (p=0.05). Uric acid concentrations increased towards the end of the radiotherapy in both response groups (p=0.02 at 50 Gy). In this study, 26.6% of the plasma TRAP was due to unidentified antioxidants (UNID).

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; Clinical Protocols; Free Radicals; Humans; Lung Neoplasms; Middle Aged; Peroxides; Predictive Value of Tests; Radiotherapy Dosage; Uric Acid; Vitamin E

Recent observational studies and meta-analyses have shown that vitamin C reduces cancer incidence and mortality, but the underlying mechanisms remain unclear. We conducted a comprehensive pan-cancer analysis and biological validation in clinical samples and animal tumor xenografts to understand its prognostic value and association with immune characteristics in various cancers.. We used the Cancer Genome Atlas gene expression data involving 5769 patients and 20 cancer types. Vitamin C index (VCI) was calculated using the expression of 11 genes known to genetically predict vitamin C levels, which were classified into high and low subgroups. The correlation between VCI and patient overall survival (OS), tumor mutational burden (TMB), microsatellite instability (MSI), and immune microenvironment was evaluated, using Kaplan-Meier analysis method and ESTIMATE (https://bioinformatics.mdanderson.org/estimate/). Clinical samples of breast cancer and normal tissues were used to validate the expression of VCI-related genes, and animal experiments were conducted to test the impact of vitamin C on colon cancer growth and immune cell infiltration.. Significant changes in expression of VCI-predicted genes were observed in multiple cancer types, especially in breast cancer. There was a correlation of VCI with prognosis in all samples (adjusted hazard ratio [AHR] = 0.87; 95% confidence interval [CI] = 0.78-0.98;. VCI is significantly correlated with OS and immunotypes in multiple cancers, and vitamin C might have therapeutic potential in colon cancer.

Topics: Animals; Ascorbic Acid; Breast Neoplasms; Carcinoma, Renal Cell; Colonic Neoplasms; Female; Humans; Kidney Neoplasms; Lung Neoplasms; Mice; Rectal Neoplasms; Tumor Microenvironment; Vitamins

High dose intravenous vitamin C (IVC) has been proposed as a pro-oxidant anticancer agent. However, there is a lack of biomarkers that are specific for this treatment. Here, we explored profiles of gene expression responding to IVC treatment in non-small cell lung cancer (NSCLC) cells as an effort for potential biomarker discovery. Genome-wide RNA-seq was performed in human NSCLC cell lines treated with pharmacological concentrations of vitamin C(VitC) for differential expression of genes. The identified genes were analyzed for correlations with patient prognosis using data from the Kaplan-Meier Plotter and the Human Protein Atlas databases. Further, tumor samples from a retrospective study of 153 NSCLC patients were analyzed with immunohistochemistry for expression of targeted genes, and patient prognosis was correlated to these genes. Two genes, namely SERPINE1 and SERPINB7 were found to be downregulated in NSCLC cells following VitC treatment. Combined patient data from the cohort analysis and online databases revealed that these 2 genes presented an unfavorable prognostic prediction of overall survival (OS) in NSCLC patients receiving standard of care. However, high expression level of these 2 genes were associated with prolonged OS in NSCLC patients receiving IVC in addition to standard of care. These data revealed that SERPINE1 and SERPINB7 have the potential to serve as predictive factors indicating favorable responses to IVC treatment in patients with NSCLC. Further validations are warranted.

Topics: Antineoplastic Agents; Ascorbic Acid; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Plasminogen Activator Inhibitor 1; Retrospective Studies; Serpins

The prognosis of patients with lung cancer accompanied by interstitial pneumonia is poorer than that of patients with lung cancer but without interstitial pneumonia. Moreover, the available therapeutic interventions for lung cancer patients with interstitial pneumonia are limited. Therefore, a new treatment strategy for these patients is required. The aim of the present study was to investigate the pathophysiological relationship between interstitial pneumonia and lung cancer and explore potential therapeutic agents.. A novel hybrid murine model of lung cancer with interstitial pneumonia was established via bleomycin-induced pulmonary fibrosis followed by orthotopic lung cancer cell transplantation into the lungs. Changes in tumor progression, lung fibrosis, RNA expression, cytokine levels, and tumor microenvironment in the lung cancer with interstitial pneumonia model were investigated, and therapeutic agents were examined. Additionally, clinical data and samples from patients with lung cancer accompanied by interstitial pneumonia were analyzed to explore the potential clinical significance of the findings.. In the lung cancer with interstitial pneumonia model, accelerated tumor growth was observed based on an altered tumor microenvironment. RNA sequencing analysis revealed upregulation of the hypoxia-inducible factor 1 signaling pathway. These findings were consistent with those obtained for human samples. Moreover, we explored whether ascorbic acid could be an alternative treatment for lung cancer with interstitial pneumonia to avoid the disadvantages of hypoxia-inducible factor 1 inhibitors. Ascorbic acid successfully downregulated the hypoxia-inducible factor 1 signaling pathway and inhibited tumor progression and lung fibrosis.. The hypoxia-inducible factor 1 pathway is critical in lung cancer with interstitial pneumonia and could be a therapeutic target for mitigating interstitial pneumonia-mediated lung cancer progression.

Topics: Animals; Ascorbic Acid; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Mice; Pneumonia; Pulmonary Fibrosis; Tumor Microenvironment

It is unclear whether diet, and in particular certain foods or nutrients, are associated with lung cancer risk. We assessed associations of 92 dietary factors with lung cancer risk in 327 790 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) per SD higher intake/day of each food/nutrient. Correction for multiple comparisons was performed using the false discovery rate and identified associations were evaluated in the Netherlands Cohort Study (NLCS). In EPIC, 2420 incident lung cancer cases were identified during a median of 15 years of follow-up. Higher intakes of fibre (HR per 1 SD higher intake/day = 0.91, 95% CI 0.87-0.96), fruit (HR = 0.91, 95% CI 0.86-0.96) and vitamin C (HR = 0.91, 95% CI 0.86-0.96) were associated with a lower risk of lung cancer, whereas offal (HR = 1.08, 95% CI 1.03-1.14), retinol (HR = 1.06, 95% CI 1.03-1.10) and beer/cider (HR = 1.04, 95% CI 1.02-1.07) intakes were positively associated with lung cancer risk. Associations did not differ by sex and there was less evidence for associations among never smokers. None of the six associations with overall lung cancer risk identified in EPIC were replicated in the NLCS (2861 cases), however in analyses of histological subtypes, inverse associations of fruit and vitamin C with squamous cell carcinoma were replicated in the NLCS. Overall, there is little evidence that intakes of specific foods and nutrients play a major role in primary lung cancer risk, but fruit and vitamin C intakes seem to be inversely associated with squamous cell lung cancer.

Topics: Ascorbic Acid; Cohort Studies; Diet; Europe; Humans; Lung Neoplasms; Netherlands; Nutrients; Prospective Studies; Risk Factors; Vitamin A

Topics: Apoptosis; Ascorbic Acid; Caspases; Cell Line, Tumor; Cell Survival; Cytochromes c; Humans; Hydrogen Peroxide; Lung Neoplasms; Membrane Potential, Mitochondrial; Polysaccharides; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Sargassum; Signal Transduction; TOR Serine-Threonine Kinases

Trans-plasma membrane electron transfer (tMPET) is a process by which reducing equivalents, either electrons or reductants like ascorbic acid, are exported to the extracellular environment by the cell. TPMET is involved in a number of physiological process and has been hypothesised to play a role in the redox regulation of cancer metabolism. Here, we use a new electrochemical assay to elucidate the 'preference' of cancer cells for different trans tPMET systems. This aids in proving a biochemical framework for the understanding of tPMET role, and for the development of novel tPMET-targeting therapeutics. We have delineated the mechanism of tPMET in 3 lung cancer cell models to show that the external electron transfer is orchestrated by ascorbate mediated shuttling via tPMET. In addition, the cells employ a different, non-shuttling-based mechanism based on direct electron transfer via Dcytb. Results from our investigations indicate that tPMETs are used differently, depending on the cell type. The data generated indicates that tPMETs may play a fundamental role in facilitation of energy reprogramming in malignant cells, whereby tPMETs are utilised to supply the necessary energy requirement when mitochondrial stress occurs. Our findings instruct a deeper understanding of tPMET systems, and show how different cancer cells may preferentially use distinguishable tPMET systems for cellular electron transfer processes.

Topics: Ascorbic Acid; Cell Line, Tumor; Cell Membrane; Cytochrome b Group; Electron Transport; Energy Metabolism; Humans; Lung Neoplasms; Oxidation-Reduction; Oxidoreductases

Ovarian cancer is the deadliest gynecological malignancy in women, and fifth leading cause of death. Despite advances made in chemotherapy and surgery, the average time of clinical remission is approximately 2 years and the 5-year survival rate is 45%. Thus, there is an urgent need for the development of a novel therapeutic approach to ovarian cancer treatment. We investigated the effect of a specific nutrient mixture (EPQ) containing ascorbic acid, lysine, proline, green tea extract, and quercetin on human ovarian cancer cell A-2780 in vivo and in vitro. Athymic female nude mice (n = 12) were all inoculated intraperitoneally (IP) with 2 × 10⁶ cells in 0.1 mL of phosphate buffered saline (PBS) and randomly divided into two groups. Upon injection, the Control group (n = 6) was fed a regular diet and the EPQ group (n = 6) a regular diet supplemented with 0.5% EPQ. Four weeks later, the mice were sacrificed and tumors that developed in the ovary were excised, weighed, and processed for histology. Lungs were inspected for metastasis. In vitro, A-2780 cells were cultured in Dulbecco modified Eagle medium supplemented with 10% FBS and antibiotics. At near confluence, cells were treated with EPQ in triplicate at concentrations between 0 and 1000 μg/mL. Cell proliferation was measured via MTT assay, MMP-9 secretion via gelatinase zymography, invasion through Matrigel and morphology via hematoxylin and eosin (H & E) staining. All Control mice developed large ovarian tumors, whereas 5 out of 6 mice in the EPQ group developed no tumors, and one, a small tumor. Control mice also showed lung metastasis in 6 out of 6 mice, while no lung metastasis was evident in EPQ mice. Zymography demonstrated only MMP-9 expression, which EPQ inhibited in a dose-dependent fashion, with virtual total block at 250 μg/mL concentration. EPQ significantly inhibited invasion through Matrigel with total block at 250 μg/mL concentration. MTT showed dose-dependent inhibition of cell proliferation with EPQ, and H & E staining showed no morphological changes below 500 μg/mL EPQ. These results suggest that EPQ has therapeutic potential in the treatment of ovarian cancer by significantly suppressing ovarian tumor incidence and growth and lung metastasis, and by inhibiting MMP-9 secretion and invasion of A-2780 ovarian cancer cells.

Topics: Animals; Antioxidants; Ascorbic Acid; Cell Line, Tumor; Cell Proliferation; Dietary Supplements; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Lysine; Matrix Metalloproteinase 9; Mice; Mice, Nude; Micronutrients; Neoplasm Metastasis; Ovarian Neoplasms; Plant Extracts; Proline; Quercetin; Tea; Xenograft Model Antitumor Assays

The lung cancer incidence in the Xuanwei and neighboring region, Yunnan, China, is among the highest in China and is attributed to severe air pollution with high benzo(a)pyrene levels. We systematically and comparatively analyzed DNA methylation alterations at genome and gene levels in Xuanwei lung cancer tissues and cell lines, as well as benzo(a)pyrene-treated cells and mouse samples. We obtained a comprehensive dataset of genome-wide cytosine-phosphate-guanine island methylation in air pollution-related lung cancer samples. Benzo(a)pyrene exposure induced multiple alterations in DNA methylation and in mRNA expressions of DNA methyltransferases and ten-11 translocation proteins; these alterations partially occurred in Xuanwei lung cancer. Furthermore, benzo(a)pyrene-induced DKK2 and EN1 promoter hypermethylation and LPAR2 promoter hypomethylation led to down-regulation and up-regulation of the genes, respectively; the down-regulation of DKK2 and EN1 promoted the cellular proliferation. Thus, DNA methylation alterations induced by benzo(a)pyrene contribute partially to abnormal DNA methylation in air pollution-related lung cancer, and these DNA methylation alterations may affect the development and progression of lung cancer. Additionally, vitamin C and B6 can reduce benzo(a)pyrene-induced DNA methylation alterations and may be used as chemopreventive agents for air pollution-related lung cancer.

Topics: Air Pollution; Animals; Anticarcinogenic Agents; Ascorbic Acid; Benzo(a)pyrene; Cell Line, Tumor; DNA Methylation; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; RNA, Messenger; Vitamin B 6

The roles of ginsenoside compound K (CK) in inhibiting tumor have been widely recognized in recent years. However, low water solubility and significant P-gp efflux have restricted its application. In this study, CK ascorbyl palmitate (AP)/d-α-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS) mixed micelles were prepared as a delivery system to increase the absorption and targeted antitumor effect of CK. Consequently, the solubility of CK increased from 35.2±4.3 to 1,463.2±153.3 μg/mL. Furthermore, in an in vitro A549 cell model, CK AP/TPGS mixed micelles significantly inhibited cell growth, induced G0/G1 phase cell cycle arrest, induced cell apoptosis, and inhibited cell migration compared to free CK, all indicating that the developed micellar delivery system could increase the antitumor effect of CK in vitro. Both in vitro cellular fluorescence uptake and in vivo near-infrared imaging studies indicated that AP/TPGS mixed micelles can promote cellular uptake and enhance tumor targeting. Moreover, studies in the A549 lung cancer xenograft mouse model showed that CK AP/TPGS mixed micelles are an efficient tumor-targeted drug delivery system with an effective antitumor effect. Western blot analysis further confirmed that the marked antitumor effect in vivo could likely be due to apoptosis promotion and P-gp efflux inhibition. Therefore, these findings suggest that the AP/TPGS mixed micellar delivery system could be an efficient delivery strategy for enhanced tumor targeting and antitumor effects.

Topics: A549 Cells; Animals; Apoptosis; Ascorbic Acid; Cell Cycle; Cell Movement; Drug Delivery Systems; Endocytosis; Ginsenosides; Humans; In Situ Nick-End Labeling; Lung Neoplasms; Mice, Nude; Micelles; Succinates; Tumor Burden; Vitamin E

Photodynamic therapy (PDT) uses light, photosensitizer molecules and oxygen to generate reactive oxygen species (ROS) that kill cancer cells. Redaporfin, a new photosensitizer in clinical trials, generates both singlet oxygen and superoxide ions. We report the potentiation of redaporfin-PDT in combination with ascorbate and with the inhibition of antioxidant enzymes in A549 (human lung adenocarcinoma) and CT26 (mouse colon adenocarcinoma) cells. The addition of ascorbate and the inhibition of superoxide dismutase (SOD) strongly increased the phototoxicity of redaporfin towards A549 cells but not towards CT26 cells. The inhibition of catalase and the depletion of the glutathione pool also potentiate redaporfin-PDT towards A549 cells. The lower SOD activity of A549 cells might explain this difference. SOD activity levels may be explored to increase the selectivity and efficacy of PDT with photosensitizers that generate radical species.

Topics: A549 Cells; Adenocarcinoma; Adenocarcinoma of Lung; Animals; Antioxidants; Ascorbic Acid; Cell Line, Tumor; Cell Survival; Humans; Hydrogen Peroxide; Light; Lung Neoplasms; Mice; Oxidative Stress; Photochemotherapy; Photosensitizing Agents; Porphyrins; Reactive Oxygen Species; Sulfonamides; Superoxide Dismutase

Chemoprevention is considered as one of the most promising and realistic approaches in the prevention of lung cancer. Chrysin, a naturally occurring dietary flavone widely found in Passiflora family of plants and honey, has been studied extensively for its chemopreventive properties. The objective of present study is to divulge the chemopreventive role of chrysin against benzo(a)pyrene [B(a)P] induced lung carcinogenesis in Swiss albino mice.. B(a)P was administered orally (50mg/kg body weight) twice a week for four weeks to induce lung cancer in mice. The body weight, lung weight, tumor incidence, lipid peroxidation, carcinoembryonic antigen, enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase) and non-enzymatic antioxidants (reduced glutathione, vitamin E and vitamin C) were estimated. Further, histopathological analysis of lung tissue and western blotting analysis of PCNA, COX-2 and NF-κB were also carried out.. Administration of B(a)P resulted in increased lipid peroxides and carcinoembryonic antigen with concomitant decrease in the levels of both enzymatic antioxidants and non-enzymatic antioxidants. Chrysin treatment (250mg/kg body weight) significantly attenuated all these changes thereby showing potent anti lung cancer effect. Further, the anticancer effect of chrysin was confirmed by histopathology of lungs, and immunoblotting analysis of PCNA, COX-2 and NF-κB, where chrysin supplementation downregulated the expression of these proteins and maintained cellular homeostasis.. Overall, these findings confirm the chemopreventive potential of chrysin against B(a)P induced lung cancer in Swiss albino mice.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Ascorbic Acid; Benzo(a)pyrene; Carcinogenesis; Catalase; Chemoprevention; Diet; Disease Models, Animal; Flavones; Flavonoids; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Lipid Peroxidation; Lung; Lung Neoplasms; Male; Mice; NF-kappa B; Superoxide Dismutase; Vitamin E

Non-thermal plasma (NTP) is a recently developed technology that elicits a variety of biological effects. This includes cancer cell-specific cytotoxicity, which is mainly attributed to the regional generation of reactive oxygen species (ROS). We studied the effects of NTP on malignant mesothelioma (MM) and its modulation by l-ascorbate. l-ascorbate is a major water-soluble anti-oxidant in vivo, but its pro-oxidant activity in vitro has been well recognized. Thus, the effects of ascorbate on the efficacy of NTP is important to examine. NTP exposure dose-dependently killed MM cells, whereas MM cells tolerated 1 mM l-ascorbate. However, brief pre-treatment with a pharmacological dose (250-750 μM) of l-ascorbate immediately prior to NTP exposure significantly increased its cytotoxicity in a dose-dependent manner, which was inhibited by the iron chelator, deferoxamine. However, paradoxically, this potentiating effect of l-ascorbate was completely abolished by a prolonged 4 h pre-incubation with l-ascorbate (500 μM). MM cytotoxicity induced by NTP was associated with immediate oxidative stress evaluated by 2',7'-dichlorodihydrofluorecein diacetate, which was followed by an increase in the expression of the autophagosome marker, LC3B-II. In conclusion, MM can be a target for NTP treatment and l-ascorbate can increase or decrease its efficacy depending on the length of the pre-incubation period.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Autophagy; Cell Line, Tumor; Cell Survival; Deferoxamine; Dose-Response Relationship, Drug; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Microscopy, Fluorescence; Oxidative Stress; Plasma Gases; Reactive Oxygen Species; Temperature

Most patients attending cancer clinics have hypovitaminosis D. Correcting or preventing this abnormal condition could mitigate the emotional and physical complications of their disease, but clinical trials of vitamin D therapy in this setting are hindered by the unavailability of safe, effective and practical loading dose regimens.. In this single arm open-label pharmacokinetic trial, outpatients with advanced lung cancer consumed 20,000 IU vitamin D daily with the largest meal of the day for 14 days followed by 10,000 IU per day for a further 7 days. Plasma concentrations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone, calcium, vitamin C and C-reactive protein were measured on protocol days 0, 14 and 21, and serum vitamin D binding protein (VDBP) concentrations on days 0 and 21. As a secondary objective, preliminary information was obtained regarding clinical effects of rapid vitamin D loading on mood and symptoms by administering appropriate questionnaires two times at baseline and after 14 and 21 days of vitamin D therapy.. Of the 91 patients enrolled in the study, 85 % had hypovitaminosis D and 41 % had hypovitaminosis C. Plasma VDBP concentrations were in the normal range. The vitamin D load increased the average plasma 25(OH)D concentration to 116 ± 34 nmol/L (mean ± SD); the median concentration was 122 nmol/L (interquartile range 103-134); VDBP concentrations did not change. Final plasma 25(OH)D concentrations were subnormal (<75 nmol/L) for 13 % of the patients and sub-target (<120 nmol/L) for 44 % of them. In most cases, subnormal and sub-target 25(OH)D concentrations were attributable to obesity and/or a low baseline 25(OH)D concentration. Mood and symptom scores did not change significantly throughout the 3-week protocol.. Hypovitaminosis D and C are very common in outpatients with advanced lung cancer. A vitamin D load of 20,000 IU per day for 14 days failed to achieve the target concentration in 44 % of the participants in this trial. These results suggest that a loading dose of 30,000 IU per day for 14 days would be safe and effective for patients who are obese or at risk of severe hypovitaminosis D. The preliminary nature of the study design, and the failure to achieve target 25(OH)D concentrations for a large proportion of the patients, do not allow any firm conclusion about the clinical effects of correcting hypovitaminosis D in this patient population. Nevertheless, no evidence was obtained that partial correction of hypovitaminosis D greatly improved mood, reduced distress or relieved cancer-related symptoms. This trial was registered at clinicaltrials.gov as NCT01631526.

Topics: Affect; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Biological Availability; C-Reactive Protein; Calcium; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Male; Middle Aged; Parathyroid Hormone; Prevalence; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

We report a case of regression of multiple pulmonary metastases, which originated from hepatocellular carcinoma after treatment with intravenous administration of high-dose vitamin C. A 74-year-old woman presented to the clinic for her cancer-related symptoms such as general weakness and anorexia. After undergoing initial transarterial chemoembolization (TACE), local recurrence with multiple pulmonary metastases was found. She refused further conventional therapy, including sorafenib tosylate (Nexavar). She did receive high doses of vitamin C (70 g), which were administered into a peripheral vein twice a week for 10 months, and multiple pulmonary metastases were observed to have completely regressed. She then underwent subsequent TACE, resulting in remission of her primary hepatocellular carcinoma.

Topics: Aged; Antineoplastic Agents; Ascorbic Acid; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Combined Modality Therapy; Female; Humans; Liver Neoplasms; Lung Neoplasms; Neoplasm Recurrence, Local; Niacinamide; Phenylurea Compounds; Sorafenib; Treatment Outcome

Studying different concentrations of nickel smelting smoke subjects of human lung adenocarcinoma cells (A549) carcinogenic effects, discusses the influence of L-ascorbic acid protection.. The A549 cells were divided into experimental and L-ascorbic acid in the intervention group. Plus exposure group concentration of nickel refining dusts were formulated 0.00, 6.25, 12.50, 25.00, 50.00, 100.00 µg/ml suspension, the intervention group on the basis of the added exposure group containing L-ascorbic acid (100 mmol/L), contact 24 h. Detection of cell viability by MTT assay. When the test substance concentration select 0.00, 25.00, 50.00, 100.00 µg/ml experiment for internal Flou-3 fluorescent probe to detect cell Ca²⁺ concentration, within DCFH-DA detect intracellular reactive oxygen (ROS) content, real-time quantitative PCR (real time, in the RT-PCR) was used to detect cell HIF-1α gene expression.. With the increase of concentration, subjects increased cell growth inhibition rate, intracellular Ca²⁺ concentration increases, ROS content increased, HIF-1α gene expression increased, differences were statistically significant (P < 0.05). After L-ascorbic acid intervention treatment, the results of the intervention group were lower than that of the experimental group, and the difference was statistically significant (P < 0.05), so L-ascorbic acid can effectively protect the nickel exposure damage to cells.. With subjects following exposure to nickel concentration increased, its effect on A549 cell damage increases, L-ascorbic acid cell damage caused by nickel has certain protective effect.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Ascorbic Acid; Calcium; Cell Line, Tumor; Cell Survival; Culture Media; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lung Neoplasms; Metallurgy; Nickel; Occupational Exposure; Protective Agents; Reactive Oxygen Species; Smoke

This study investigated the δ-aminolevulinate dehydratase (δ-ALA-D) activity in whole blood as well as the parameters of oxidative stress, such as reactive species (RS) levels in serum, thiobarbituric acid reactive substances (TBARS) levels, the superoxide dismutase (SOD) and catalase (CAT) activities, as well as total thiols (T-SH) and non-protein thiols (NPSH) levels in platelets. Moreover, the content of vitamin C and E in plasma and serum, respectively, in lung cancer patients was also investigated. We collected blood samples from patients (n=28) previously treated for lung cancer with chemotherapy. Patients were classified as stage IIIb and IV according to the Union for International Cancer Control (UICC). Results showed a decrease of 37% in δ-ALA-D activity in patients with lung cancer when compared to the control group. RS and TBARS levels were 8% and 99% higher in the patient group, respectively. The activity of SOD and CAT as well as the vitamin C content were 41%, 35% and 127% lower in patients when compared with controls, respectively. However, T-SH and vitamin E levels were 27% and 44% higher in lung cancer patients, respectively. Results show that the overproduction of reactive species in patients with lung cancer may be interfering with the activity of δ-ALA-D. Likewise, the decrease in the activity of this enzyme may be contributing for the oxidative stress.

Topics: Aged; Ascorbic Acid; Blood Platelets; Case-Control Studies; Catalase; Cisplatin; Deoxycytidine; Female; Gemcitabine; Humans; Lung Neoplasms; Male; Middle Aged; Oxidative Stress; Porphobilinogen Synthase; Reactive Oxygen Species; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

In Poland lung cancer is the most commonly occurring cancer type, both in men and women. Among the most important concerns related to this disease are clinical symptoms caused by deteriorating physical condition and intolerance to chemotherapy. The aim of this work was the assessment of the clinical symptoms and treatment tolerance in patients with non-small cell lung cancer (NSCLC) undergoing first-line chemotherapy and pulmonary rehabilitation.. 90 patients with inoperable NSCLC have undergone the examination. This included 69 men and 21 women aged between 46-75 years (average age 61.5 +/- 8.2 years). These were divided into 3 groups: group 1--30 patients undergoing standard chemotherapy; group II--30 patients undergoing standard chemotherapy and pulmonary rehabilitation; group Ill--30 patients undergoing standard chemotherapy and pulmonary rehabilitation with additional vitamin C supplementation. Clinical symptoms intensification was assessed using the ESAS scale (Edmonton Symptom Assessment System), by comparing the initial score with that after 6 weeks of chemotherapy in each individual.. In groups II and III, where pulmonary rehabilitation was carried out, the intensification of the clinical symptoms and lowering of the tolerance for the treatment after 6 weeks of first-line chemotherapy were significantly lower (p < 0.05) than in group I. CONCLUSIONS. Pulmonary rehabilitation significantly limits the side effects of chemotherapy and the deterioration of the state of patients with NSCLC. Simultaneous supplementation with ascorbic acid increases the positive effects of pulmonary rehabilitation in those patients.

Topics: Aged; Antineoplastic Agents; Ascorbic Acid; Carcinoma, Non-Small-Cell Lung; Dietary Supplements; Female; Humans; Lung Neoplasms; Male; Middle Aged

Indoleamine 2,3-dioxygenase (IDO-1) is emerging as an important new therapeutic target for the treatment of cancer, neurological disorders, and other diseases that are characterized by pathological tryptophan metabolism. However, only a few structural classes are known to be IDO-1 inhibitors. In this study, a natural compound tryptanthrin was discovered to be a novel potent IDO-1 inhibitor by screening of indole-based structures. Three series of 13 tryptanthrin derivatives were synthesized, and the structure-activity analysis was undertaken. The optimization led to the identification of 5c, which exhibited the inhibitory activity at a nanomolar level. In vitro 5c dramatically augmented the proliferation of T cells. When administered to Lewis lung cancer (LLC) tumor-bearing mice, 5c significantly inhibited IDO-1 activity and suppressed tumor growth. In addition, 5c reduced the numbers of Foxp3(+) regulatory T cells (Tregs), which are known to prevent the development of efficient antitumor immune responses.

Topics: Animals; Antineoplastic Agents; Carcinoma, Lewis Lung; Dose-Response Relationship, Drug; Drug Discovery; Enzyme Inhibitors; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Lung Neoplasms; Mice; Molecular Structure; Quinazolines; Structure-Activity Relationship; Xenograft Model Antitumor Assays

Malignant pleural mesothelioma (MPM) is a poor prognosis disease lacking adequate therapy. We have previously shown that ascorbic acid administration is toxic to MPM cells. Here we evaluated a new combined therapy consisting of ascorbate/epigallocatechin-3-gallate/gemcitabine mixture (called AND, for Active Nutrients/Drug). In vitro effects of AND therapy on various MPM cell lines revealed a synergistic cytotoxic mechanism. In vivo experiments on a xenograft mouse model for MPM, obtained by REN cells injection in immunocompromised mice, showed that AND strongly reduced the size of primary tumor as well as the number and size of metastases, and prevented abdominal hemorrhage. Kaplan Meier curves and the log-rank test indicated a marked increase in the survival of AND-treated animals. Histochemical analysis of dissected tumors showed that AND induced a shift from cell proliferation to apoptosis in cancer cells. Lysates of tumors from AND-treated mice, analyzed with an antibody array, revealed decreased TIMP-1 and -2 expressions and no effects on angiogenesis regulating factors. Multiplex analysis for signaling protein phosphorylation exhibited inactivation of cell proliferation pathways. The complex of data showed that the AND treatment is synergistic in vitro on MPM cells, and blocks in vivo tumor progression and metastasization in REN-based xenografts. Hence, the AND combination is proposed as a new treatment for MPM.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Catechin; Cell Line, Tumor; Cell Proliferation; Deoxycytidine; Drug Synergism; Gemcitabine; Humans; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Mice; Mice, Inbred NOD; Mice, SCID; Pleural Neoplasms; Signal Transduction; Xenograft Model Antitumor Assays

Ascorbic acid (AA) exhibits significant anticancer activity at pharmacologic doses achievable by parenteral administration that have minimal effects on normal cells. Thus, AA has potential uses as a chemotherapeutic agent alone or in combination with other therapeutics that specifically target cancer-cell metabolism. We compared the effects of AA and combinations of AA with the glycolysis inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3-PO) on the viability of three non-small cell lung cancer (NSCLC) cell lines to the effects on an immortalized lung epithelial cell line. AA concentrations of 0.5 to 5 mM caused a complete loss of viability in all NSCLC lines compared to a <10% loss of viability in the lung epithelial cell line. Combinations of AA and 3-PO synergistically enhanced cell death in all NSCLC cell lines at concentrations well below the IC50 concentrations for each compound alone. A synergistic interaction was not observed in combination treatments of lung epithelial cells and combination treatments that caused a complete loss of viability in NSCLC cells had modest effects on normal lung cell viability and reactive oxygen species (ROS) levels. Combination treatments induced dramatically higher ROS levels compared to treatment with AA and 3-PO alone in NSCLC cells and combination-induced cell death was inhibited by addition of catalase to the medium. Analyses of DNA fragmentation, poly (ADP-ribose) polymerase cleavage, annexin V-binding, and caspase activity demonstrated that AA-induced cell death is caused via the activation of apoptosis and that the combination treatments caused a synergistic induction of apoptosis. These results demonstrate the effectiveness of AA against NSCLC cells and that combinations of AA with 3-PO synergistically induce apoptosis via a ROS-dependent mechanism. These results support further evaluation of pharmacologic concentrations of AA as an adjuvant treatment for NSCLC and that combination of AA with glycolysis inhibitors may be a promising therapy for the treatment of NSCLC.

Topics: Antineoplastic Agents; Apoptosis; Ascorbic Acid; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Survival; Drug Synergism; Glycolysis; Humans; Lung Neoplasms

Immunotherapy has become an attractive new strategy in the treatment of cancer. The laboratory and clinical study of cancer immunotherapy is rapidly advancing. However, in the clinical setting, the results of cancer immunotherapy are mixed. We therefore contend that cancer immunotherapy should be customized to each patient individually based on their immune status and propose an integrative immunotherapy approach with second-generation group-specific component macrophage activating factor (GcMAF)-containing human serum.. The standard protocol of our integrative cancer immunotherapy is as follows: i) 0.5 ml GcMAF-containing human serum is administered intramuscularly or subcutaneously once or twice per week for the duration of cancer therapy until all cancer cells are eradicated; ii) hyper T/natural killer (NK) cell therapy is given once per week for six weeks; iii) high-dose vitamin C is administered intravenously twice per week; iv) alpha lipoic acid (600 mg) is administered orally daily; v) vitamin D3 (5,000-10,000 IU) is administered orally daily.. By March 2013, Saisei Mirai have treated over 345 patients with GcMAF. Among them we here present the cases of three patients for whom our integrative immunotherapy was remarkably effective.. The results of our integrative immunotherapy seem hopeful. We also plan to conduct a comparative clinical study.>

Topics: Aged; Ascorbic Acid; Bone Neoplasms; Cell- and Tissue-Based Therapy; Combined Modality Therapy; Female; Humans; Immunotherapy; Injections, Intramuscular; Injections, Subcutaneous; Liver Neoplasms; Lung Neoplasms; Macrophage-Activating Factors; Male; Prognosis; Prostatic Neoplasms; Thioctic Acid; Thymus Neoplasms; Vitamin D-Binding Protein

Tea polyphenols (-)-epigallocatechin-3-gallate (EGCG) and theaflavin-3-3'-digallate (TF3) are two prospective compounds in cancer prevention and treatment. Ascorbic acid (Vc) is essential to a healthy diet as well as being a highly effective antioxidant. In this work, the effects of the combination of EGCG or TF3 with Vc on the apoptosis and caspases-3/9 activities in human lung adenocarcinoma SPC-A-1 cells and esophageal carcinoma Eca-109 cells were determined. Furthermore, the role of mitogen-activated protein kinases (MAPK) pathways in the apoptosis induced by TF3 or EGCG together with Vc were studied using three MAPK inhibitors (ERK inhibitor PD98059, JNK inhibitor SP600125 and p38 inhibitor SB203580). Our results showed that Vc could enhance the EGCG and TF3 induced apoptosis in SPC-A-1 and Eca-109 cells, and this effect involved the activation of caspase-3 and 9. EGCG, TF3 and Vc could activate MAPK pathways respectively, and each compound activated different MAPK subfamilies in different cells. This may explain the enhancement of EGCG and TF3 induced apoptosis by Vc in SPC-A-1 and Eca-109 cells, and will ultimately aid the design of more effective anti-cancer treatments.

Topics: Adenocarcinoma; Anticarcinogenic Agents; Antineoplastic Agents; Apoptosis; Ascorbic Acid; Biflavonoids; Caspase 3; Caspase 9; Catechin; Cell Line, Tumor; Enzyme Inhibitors; Esophageal Neoplasms; Gallic Acid; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; MAP Kinase Signaling System

Lung cancer is one of the most common cancer types and it usually takes the form of non-small cell lung cancer (NSCLC). ROS take part in the process of carcinogenesis. What more, chemotherapy used in cancer treatment augments their production, leading to the weakening of the antioxidative barrier. As a result in cancer patients undergoing chemotherapy the reduction-oxidation processes are imbalanced. Vitamins A, C and E form an important part of the nonenzymatic antioxidative barrier in humans. THE AIM OF THE STUDY was an assessment of concentrations of A, C and E vitamins in the plasma of patients with NSCLC before and after chemotherapy. 25 first-line chemotherapy patients with inoperable NSCLC have undergone examination, including 20 men and 5 women aged between 50-75 years (average age 62.6 +/- 6.1 years). 24 healthy individuals including 18 men and 6 women aged between 49-71 years (average age 59.5 +/- 6.6 years) formed a control group. In cancer patients the concentration of vitamins A, C and E was assessed by spectrophotometry using T60V spectrophotometer (PG Instruments) before and after first-line chemotherapy, while in control group it was assessed only once.. The concentration of A, C and E vitamins in plasma of NSCLC patients was lower (p < 0.05) than in the control group. After 6 weeks of chemotherapy another significant drop in vitamin concentrations in NSCLC patients was observed (p < 0.05) and was biggest for vitamin C (39.1%).. Lowering of A, C and E vitamins concentrations in the plasma of NSCLCpatients suggests a weakening of antioxidative barrier. Chemotherapy leads to further fall in the concentration of those vitamins in patients' plasma.

Topics: Antineoplastic Agents; Ascorbic Acid; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Middle Aged; Vitamin A; Vitamin E

Most epidemiological studies evaluating the association of fruit and vegetable intakes on lung cancer risk were conducted in North American and European countries. We investigated the association of intakes of fruits, vegetables, dietary vitamins A and C, and folate with lung cancer risk among 61,491 adult Chinese men who were recruited into the Shanghai Men's Health Study, a population-based, prospective cohort study. Baseline dietary intake was assessed through a validated food frequency questionnaire during in-home visits. Multivariate Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of lung cancer risk associated with dietary intakes. During a median follow-up of 5.5 yr, 359 incident lung cancer cases accrued after the first year of follow-up and 68.8% of them were current smokers. Intakes of green leafy vegetables, β-carotene-rich vegetables, watermelon, vitamin A, and carotenoids were inversely associated with lung cancer risk; the corresponding HR (95% CI) comparing the highest with the lowest quartiles were 0.72 (0.53-0.98), 0.69 (0.51-0.94), 0.65 (0.47-0.90), 0.63 (0.44-0.88), and 0.64 (0.46-0.88). Intake of all fruits and vegetables combined was marginally associated with lower risk. Our study suggests that the consumption of carotenoid-rich vegetables is inversely associated with lung cancer risk.

Topics: Adult; Aged; Ascorbic Acid; Carotenoids; China; Cohort Studies; Eating; Folic Acid; Follow-Up Studies; Fruit; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Risk Factors; Vegetables; Vitamin A; Vitamins

Chemoprevention is regarded as one of the most promising and realistic approaches in the prevention of cancer. All-trans retinoic acid (ATRA) is an active metabolite of vitamin A under the family retinoids, derived by irreversible oxidation of retinol (vitamin A), the parent compound for all natural retinoids. The aim of the present study is to divulge the chemopreventive and chemoprotective nature of ATRA during benzo(a)pyrene (B(a)P) induced lung cancer development in BALB/c mice. Administration of B(a)P (50 mg/kg body weight) to mice resulted in increased lipid peroxides (LPO), lipid hydroperoxides (LOOH) and nitric oxide (NO) with concomitant decrease in the levels of tissue anti-oxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and vitamin C. ATRA supplementation (0.585 mg/kg body weight) attenuated all these alterations, which indicates the anti-cancer effect that was further confirmed by histopathological analysis. Overall, the above data show that the anti-cancer effect of ATRA is more pronounced when used as an chemopreventive agent against B(a)P-induced lung carcinogenesis.

Topics: Animals; Ascorbic Acid; Behavior, Animal; Benzo(a)pyrene; Catalase; Chemoprevention; Glutathione; Glutathione Peroxidase; Lipid Peroxidation; Lipid Peroxides; Liver; Lung; Lung Neoplasms; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Nitric Oxide; Oxidative Stress; Superoxide Dismutase; Treatment Outcome; Tretinoin

Birth is characterized by an intense oxidative stress resulting in nucleotide alterations and gene overexpression in mouse lung. We showed that cigarette smoke (CS) is carcinogenic when exposure starts soon after birth and applied this bioassay to evaluate the efficacy of chemopreventive agents. The present study evaluated whether administration of the antioxidants N-acetyl-L-cysteine (NAC) and vitamin C or ascorbic acid (AsA) during pregnancy can protect strain H Swiss mice exposed to CS after birth. Exposure to CS, for 4 months, of newborns from untreated mice resulted in significant alterations at 8 months of life, including alveolar epithelial hyperplasia, emphysema, blood vessel proliferation, microadenomas, adenomas, and malignant tumors in lung, liver parenchymal degeneration and urinary bladder epithelium hyperplasia. Treatment throughout pregnancy with either NAC, a scavenger of reactive oxygen species, or AsA, an electron donor, did not affect fertility, parity, and body weight of newborns. Prenatal antioxidants significantly inhibited most lesions in adult mice exposed to CS since birth. For instance, the incidence of emphysema was reduced from 27.5% in CS-exposed mice that were untreated during pregnancy to 7.1% and 14.0% in those treated prenatally with NAC and AsA, respectively. Lung adenomas were reduced from 34.8% to 16.7% and 9.3%, respectively. Malignant lung tumors were reduced from 13.0% to 4.7% by prenatal AsA. Liver parenchymal degeneration was reduced from 58.0% to 14.3% by prenatal NAC. These data mechanistically support a "transplacental chemoprevention" strategy, aimed at protecting the newborn from oxidative stress and the adult from CS-related diseases appearing later in life.

Topics: Acetylcysteine; Animals; Animals, Newborn; Antioxidants; Ascorbic Acid; Body Weight; Female; Lung Neoplasms; Maternal-Fetal Exchange; Mice; Nicotiana; Placenta; Pregnancy; Reactive Oxygen Species; Smoke; Survival

Sulfonamides of halogenated bacteriochlorins bearing Cl or F substituents in the ortho positions of the phenyl rings have adequate properties for photodynamic therapy, including strong absorption in the near-infrared (λ(max) ≈ 750 nm, ε ≈ 10(5) M(-1) cm(-1)), controlled photodecomposition, large cellular uptake, intracellular localization in the endoplasmic reticulum, low cytotoxicity, and high phototoxicity against A549 and S91 cells. The roles of type I and type II photochemical processes are assessed by singlet oxygen luminescence and intracellular hydroxyl radical detection. Phototoxicity of halogenated sulfonamide bacteriochlorins does not correlate with singlet oxygen quantum yields and must be mediated both by electron transfer (superoxide ion, hydroxyl radicals) and by energy transfer (singlet oxygen). The photodynamic efficacy is enhanced when cellular death is induced by both singlet oxygen and hydroxyl radicals.

Topics: Adenocarcinoma; Antioxidants; Ascorbic Acid; Cell Survival; Energy Transfer; Fluorescence; Humans; Hydroxyl Radical; In Vitro Techniques; Lung Neoplasms; Melanoma; Photochemotherapy; Photosensitizing Agents; Porphyrins; Reactive Oxygen Species; Singlet Oxygen; Tumor Cells, Cultured

The molecular basis of interaction of selected carotenoids and xanthophylls with ascorbic acid on cancer cells was studied to determine their anticancer effects.. Drug accumulation was measured in a human ABCB1 gene-transfected mouse lymphoma cell line and in a human lung cancer cell line by flow cytometry; furthermore, their anticancer effects were determined in mice in vivo.. Several carotenoids inhibited the multidrug resistance of cancer cells. Ascorbic acid improved the effect of certain xanthophylls, but the effect of capsanthin was not modified. Capsanthin had weak (12%) but capsorubin (85%) had a remarkable antiproliferative effect on A549 lung cancer cells. Capsorubin reduced immediate-early tumor antigen expression, while capsanthin was not effective. Capsorubin accumulates selectively in the nuclei of cancer cells.. The Authors suggest a special complex formation between membrane-bound capsorubin and ascorbic acid, which can be exploited in experimental chemotherapy.

Topics: Animals; Ascorbic Acid; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters; Cell Line, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Humans; Lung Neoplasms; Lymphoma, T-Cell; Male; Mice; Mice, Inbred CBA; Neoplasms; Pancreatic Neoplasms; Transfection; Xanthophylls; Xenograft Model Antitumor Assays

Lysosomal photosensitizers have been used in photodynamic therapy. The combination of such photosensitizers and light causes lysosomal photodamage, inducing cell death. Lysosomal disruption can lead to apoptosis but its signaling pathways remain to be elucidated. In this study, N-aspartyl chlorin e6 (NPe6), an effective photosensitizer that preferentially accumulates in lysosomes, was used to study the mechanism of apoptosis caused by lysosomal photodamage. Apoptosis in living human lung adenocarcinoma cells (ASTC-a-1) after NPe6-photodynamic treatment (NPe6-PDT) was studied using real-time single-cell analysis. Our results demonstrated that NPe6-PDT induced rapid generation of reactive oxygen species (ROS). The photodynamically produced ROS caused a rapid destruction of lysosomes, leading to release of cathepsins, and the ROS scavengers vitamin C and NAC prevent the effects. Then the following spatiotemporal sequence of cellular events was observed during cell apoptosis: Bcl-2-associated X protein (Bax) activation, cytochrome c release, and caspase-9/-3 activation. Importantly, the activation of Bax proved to be a crucial event in this apoptotic machinery, because suppressing the endogenous Bax using siRNA could significantly inhibit cytochrome c release and caspase-9/-3 activation and protect the cell from death. In conclusion, this study demonstrates that PDT with lysosomal photosensitizer induces Bax activation and subsequently initiates the mitochondrial apoptotic pathway.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Apoptosis; Ascorbic Acid; bcl-2-Associated X Protein; Caspase 3; Caspase 9; Cathepsins; Cell Line, Tumor; Cytochromes c; Fluorescent Antibody Technique; Humans; Lung Neoplasms; Lysosomes; Microscopy, Confocal; Mitochondria; Photosensitizing Agents; Porphyrins; Reactive Oxygen Species; RNA Interference; RNA, Small Interfering

Malignant mesothelioma (MMe) is a lethal tumor arising from the mesothelium of serous cavities as a result of exposure to asbestos. Current clinical standards consist of combined treatments, but an effective therapy has not been established yet and there is an urgent need for new curative approaches. Ascorbate is a nutrient that is also known as a remedy in the treatment of cancer. In the present study, we have tested the cytotoxicity of ascorbate to MMe cells in combination with drugs used in MMe therapy, such as cisplatin, etoposide, gemcitabine, imatinib, paclitaxel, and raltitrexed, as well as with promising antitumor compounds like taurolidine, α-tocopherol succinate, and epigallocatechin-3-gallate (EGCG). Dose-response curves obtained for each compound by applying the neutral red uptake (NRU) assay to MMe cells growing in vitro, allowed to obtain IC50 values for each compound used singularly. Thereafter, NRU data obtained from each ascorbate/drug combination were analyzed through Tallarida's isobolograms at the IC50 level (Tallarida, 2000), revealing synergistic interactions for ascorbate/gemcitabine and ascorbate/EGCG. These results were further confirmed through comparisons between theoretical additivity IC50 and observed IC50 from fixed-ratio dose-response curves, and over a broad range of IC levels, by using Chou and Talalay's combination index (Chou and Talalay, 1984). Synergistic interactions were also shown by examining apoptosis and necrosis rates, using the caspase 3 and lactic dehydrogenase assays, respectively. Hence, data indicate that ascorbate/gemcitabine and ascorbate/EGCG affect synergistically the viability of MMe cells and suggest their possible use in the clinical treatment of this problematic cancer.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Catechin; Cell Line, Tumor; Cell Proliferation; Cell Survival; Coloring Agents; Deoxycytidine; Drug Synergism; Gemcitabine; Humans; L-Lactate Dehydrogenase; Lung Neoplasms; Mesothelioma; Neutral Red

Vitamin C in combination with vitamin K3 (vit CK3) has been shown to inhibit tumor growth and lung metastasis in vivo, but the mechanism of action is poorly understood. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma (LLC) for 9 days before injection (i.p.) with low-dose (100 mg vit C/kg + 1 mg vit K3/kg), high-dose (1,000 mg vit C/kg + 10 mg vit K3/kg) vit CK3 twice a week for an additional 28 days. As expected, vit CK3 or cisplatin (6 mg/kg, as a positive control) significantly and dose-dependently inhibited tumor growth and lung metastasis in LLC-bearing mice. Vit CK3 restored the body weight of tumor-bearing mice to the level of tumor-free mice. Vit CK3 significantly decreased activities of plasma metalloproteinase (MMP)-2, -9, and urokinase plasminogen activator (uPA). In lung tissues, vit CK3 1) increased protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, nonmetastatic protein 23 homolog 1 and plasminogen activator inhibitor-1; 2) reduced protein expression of MMP-2 and MMP-9; and 3) inhibited the proliferating cell nuclear antigen (PCNA). These results demonstrate that vit CK3 inhibits primary tumor growth and exhibits antimetastastic potential in vivo through attenuated tumor invasion and proliferation.

Topics: Animals; Ascorbic Acid; Blotting, Western; Carcinoma, Lewis Lung; Cell Line; Cell Line, Tumor; Cell Proliferation; Cisplatin; Dose-Response Relationship, Drug; Lung Neoplasms; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Neoplasm Invasiveness; Plasminogen Activator Inhibitor 1; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Transplantation, Heterologous; Urokinase-Type Plasminogen Activator; Vitamin K 3

The role of micronutrients in lung cancer prevention is controversial, as observational and experimental studies have generated contradicting results. These discrepancies between studies may be due to different effects of micronutrients depending on source (diet or supplements). The objective of this study was to evaluate the association between vitamin C, E, folate and beta-carotene and lung cancer risk while focusing on source-specific effects of dietary and supplemental intake. The association was evaluated in a cohort of 55,557 Danes who completed a food frequency questionnaire including information on consumption of vitamin C, E, folate and beta-carotene from diet and supplements. Incidence rate ratios of lung cancer were calculated using Cox proportional hazards models. During a median follow-up of 10.6 years, 721 incident lung cancer cases were diagnosed. We found a significant protective effect of dietary vitamin E intake and a significantly higher lung cancer risk with supplemental beta-carotene and dietary folate intake. All three micronutrients exhibited significant source-specific effects. The harmful effect of dietary folate is, however, most likely to be due to uncontrolled confounding. Our results indicate source-specific effects of vitamin E and beta-carotene in lung cancer prevention with a preventive effect of dietary vitamin E and a harmful effect of supplemental beta-carotene. Future studies on micronutrients and lung cancer should take source into account.

Topics: Aged; Anticarcinogenic Agents; Ascorbic Acid; beta Carotene; Cohort Studies; Denmark; Diet; Dietary Supplements; Female; Folic Acid; Humans; Lung Neoplasms; Male; Micronutrients; Middle Aged; Proportional Hazards Models; Vitamin E

Gallic acid (GA) widely distributed in plants and foods has its various biological effects. Here, we investigated the anti-cancer effects of GA on Calu-6 and A549 lung cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH). GA dose-dependently decreased the growth of Calu-6 and A549 cells with an IC(50) of approximately 10-50 microM and 100-200 microM GA at 24h, respectively. GA also induced cell death in lung cancer cells, which was accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)). The percents of MMP (DeltaPsi(m)) loss and death cells were lower in A549 cells than Calu-6 cells. GA increased ROS levels including O(2)(-) in lung cancer cells at 24h and also GSH depleted cell numbers at this time. N-acetyl-cysteine (NAC; a well-known antioxidant) intensified growth inhibition and death in GA-treated lung cancer cells. NAC changed ROS levels and increased GSH depletion in these cells. Vitamin C significantly attenuated cell death, ROS levels and GSH depletion in GA-treated lung cancer cells. L-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) slightly enhanced growth inhibition and death in GA-treated lung cancer cells and also mildly increased ROS levels and GSH depletion in these cells. In conclusion, GA inhibited the growth of lung cancer cells. GA-induced lung cancer cell death was related to GSH depletion as well as ROS level changes.

Topics: Acetylcysteine; Antineoplastic Agents; Ascorbic Acid; Buthionine Sulfoximine; Cell Death; Cell Line, Tumor; Cell Proliferation; Gallic Acid; Glutathione; Humans; Lung Neoplasms; Oxidative Stress; Reactive Oxygen Species

Tea polyphenols have been shown to have anticancer activity in many studies. In the present study, we investigated effects of theaflavin-3-3'-digallate (TF(3)), one of the major theaflavin monomers in black tea, in combination with ascorbic acid (AA), a reducing agent, and (-)-epigallocatechin-3-gallate (EGCG), the main polyphenol presented in green tea, in combination with AA on cellular viability and cell cycles of the human lung adenocarcinoma SPC-A-1 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay showed that the 50% inhibition concentrations (IC(50)) of TF(3), EGCG, and AA on SPC-A-1 cells were 4.78, 4.90, and 30.62 micromol/L, respectively. The inhibitory rates of TF(3) combined with AA (TF(3)+AA) and EGCG combined with AA (EGCG+AA) at a molar ratio of 1:6 on SPC-A-1 cells were 54.4% and 45.5%, respectively. Flow cytometry analysis showed that TF(3)+AA and EGCG+AA obviously increased the cell population in the G(0)/G(1) phase of the SPC-A-1 cell cycle from 53.9% to 62.8% and 60.0%, respectively. TF(3)-treated cells exhibited 65.3% of the G(0)/G(1) phase at the concentration of its IC(50). Therefore, TF(3)+AA and EGCG+AA had synergistic inhibition effects on the proliferation of SPC-A-1 cells, and significantly held SPC-A-1 cells in G(0)/G(1) phase. The results suggest that the combination of TF(3) with AA or EGCG with AA enhances their anticancer activity.

Topics: Adenocarcinoma; Apoptosis; Ascorbic Acid; Cell Line, Tumor; Dose-Response Relationship, Drug; Flavonoids; Humans; Lethal Dose 50; Lung Neoplasms; Phenols; Plant Extracts; Polyphenols; Tea

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Colorectal Neoplasms; Confounding Factors, Epidemiologic; Dietary Supplements; Female; Folic Acid; Humans; Incidence; Lung Neoplasms; Male; Neoplasms; Primary Prevention; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Assessment; Selenium; United States; Vitamin B 12; Vitamin B 6; Vitamin E

Topics: Aged; Anticarcinogenic Agents; Ascorbic Acid; Clinical Trials, Phase II as Topic; Colorectal Neoplasms; Dietary Supplements; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasms; Physicians; Prostatic Neoplasms; Randomized Controlled Trials as Topic; United States; Vitamin E

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

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

Topics: Aged; Ascorbic Acid; Chemoprevention; Diet; Dietary Supplements; Female; Folic Acid; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Risk Assessment; Risk Factors; Smoking; Vitamin E; Vitamins

Lung cancer is the leading cause of cancer-related mortality in the United States. Although supplements are used by half the population, limited information is available about their specific effect on lung cancer risk.. To explore the association of supplemental multivitamins, vitamin C, vitamin E, and folate with incident lung cancer.. Prospective cohort of 77,721 men and women aged 50-76 years from Washington State in the VITAL (VITamins And Lifestyle) study. Cases were identified through the Seattle-Puget Sound SEER (Surveillance, Epidemiology, and End Results) cancer registry.. Hazard ratios (HRs) for incident lung cancer according to 10-year average daily use of supplemental multivitamins, vitamin C, vitamin E, and folate. A total of 521 cases of lung cancer were identified. Adjusting for smoking, age, and sex, there was no inverse association with any supplement. Supplemental vitamin E was associated with a small increased risk of lung cancer (HR, 1.05 for every 100-mg/d increase in dose; 95% confidence interval [CI], 1.00-1.09; P = 0.033). This risk of supplemental vitamin E was largely confined to current smokers (HR, 1.11 for every 100-mg/d increase; 95% CI, 1.03-1.19; P < 0.01) and was greatest for non-small cell lung cancer (HR, 1.07 for every 100-mg/d increase; 95% CI, 1.02-1.12; P = 0.004).. Supplemental multivitamins, vitamin C, vitamin E, and folate were not associated with a decreased risk of lung cancer. Supplemental vitamin E was associated with a small increased risk. Patients should be counseled against using these supplements to prevent lung cancer.

Topics: Aged; Ascorbic Acid; Chemoprevention; Diet; Dietary Supplements; Female; Folic Acid; Humans; Lung Neoplasms; Male; Middle Aged; Vitamin E; Vitamins

Reactive oxygen species produced either endogenously or exogenously can attack lipids, proteins and DNA in human cells and cause potentially deleterious consequences. In recent years, their role in the pathogenesis of lung cancer and the preventive effect of antioxidants have been studied extensively. In this study, our aim was to investigate the levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) and malondialdehyde as a marker for the effects of reactive oxygen species on DNA and lipids, the levels of antioxidant vitamins and the correlations between these oxidative stress markers and antioxidants in lung cancer.. Serum malondialdehyde, beta-carotene, retinol, and vitamins C and E were measured by high-performance liquid chromatography methods in fasting blood samples and 8OHdG was measured by gas chromatography-mass spectrometry in 24-h urine samples of patients with lung cancer (n=39) and healthy controls (n=31).. The levels of 8OHdG and malondialdehyde were significantly higher (p<0.05 and p<0.005, respectively) and beta-carotene, retinol, and vitamins C and E (p<0.0001, p<0.0001, p<0.0001, and p<0.05, respectively) were significantly lower in patients than in controls. There was a significantly positive correlation between 8OHdG and malondialdehyde (r=0.463, p=0.01) and a negative correlation between the levels of 8OHdG and retinol (r=-0.419, p=0.021) in the patient group.. Our results demonstrate that the oxidant/antioxidant balance was spoiled in favor of lipid peroxidation and DNA damage in lung cancer patients. Significant increases in the levels of malondialdehyde and 8OHdG and decreases in the levels of antioxidants suggest the possible involvement of oxidative stress in lung cancer.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Case-Control Studies; Chromatography, High Pressure Liquid; Deoxyguanosine; DNA Damage; Female; Humans; Lipid Peroxidation; Lung Neoplasms; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Reactive Oxygen Species; Reference Values; Vitamin A; Vitamin E; Vitamins

The effect of a pungent ingredient of red pepper, capsaicin, on oxidative stress induced changes in the antioxidant defense system by benzo(a)pyrene in the lungs of mice was studied. Oral gavage administration of benzo(a)pyrene (50 mg/kg body weight) to mice led to a marked increase in oxidative stress indicated by alterations in pulmonary lipid peroxidation, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase) and non-enzymic antioxidants (reduced glutathione, vitamin C, vitamin E and vitamin A). Pre-co-treatment with capsaicin (10 mg/kg body weight i.p.) restored cellular normalcy, highlighting the antioxidant potential of capsaicin in mitigating the oxidative stress mediated damage produced during benzo(a)pyrene-induced lung cancer.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzo(a)pyrene; Capsaicin; Catalase; Glucosephosphate Dehydrogenase; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Lipid Peroxidation; Lung; Lung Neoplasms; Male; Mice; Oxidative Stress; Superoxide Dismutase; Vitamin A; Vitamin E

Insulin-like growth factor 1 (IGF-1) and its major binding protein, IGF binding protein 3 (IGFBP-3) are implicated in lung cancer and other malignancies. We have previously shown that the combination of three major antioxidants [beta-carotene (BC), alpha-tocopherol (AT) and ascorbic acid (AA)] can prevent lung carcinogenesis in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-treated and smoke-exposed (SM) ferret model, which is highly analogous to humans. The present study is aimed at determining the effect of the combination of BC, AT and AA on antioxidant capacity, lymphocyte DNA damage, plasma IGF-1 and IGFBP-3 concentrations, as well as on IGF-1/IGFBP-3 mRNA expression in the tissues (lung and liver) of the ferrets. Ferrets were treated with or without combined antioxidant (BC, AT and AA) supplementation (AOX) for 6 months in the following 4 groups: (i) control; (ii) SM+NNK; (iii) AOX; and (iv) SM+NNK+AOX. Combined AOX supplementation significantly attenuated SM+NNK induced lymphocyte DNA damage in the ferret, while increasing resistance to oxidative damage when challenged with H(2)O(2) in vitro. Ferrets treated with SM+NNK had significantly lower IGFBP-3 mRNA expression in lungs, whereas there was significantly higher IGFBP-3 mRNA expression in the liver, as well as higher circulating IGFBP-3 concentrations. Combined AOX supplementation did not affect the plasma or tissue (lung and liver) ratio of IGF-1/IGFBP-3. Combined antioxidant supplementation provides protection against smoke-induced oxidative DNA damage, but does not affect the IGF-1/IGFBP-3 system. Differential expression of IGFBP-3 in different tissues indicates that caution should be taken when using plasma IGFBP-3 as a biomarker of tissue status.

Topics: Animals; Antioxidants; Ascorbic Acid; beta Carotene; Disease Models, Animal; DNA Breaks, Single-Stranded; Ferrets; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Liver; Lung; Lung Neoplasms; Male; Nitrosamines; Smoke; Vitamin E

In this study, we examined oxidative stress and B vitamins status in non-small cell lung cancer (NSCLC) patients at different stages. NSCLC patients were divided into 2 groups, stage III (IIIA + IIIB, n = 27) and stage IV (n = 23). A total of 16 healthy control subjects were included for comparison. Plasma levels of alpha-tocopherol, beta-carotene, vitamin C, Se, Cu, Zn, reduced glutathione (GSH), oxidized glutathione (GSSG), lipid oxidation and the activities of glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase, and xanthine oxidase (XO) were determined for evaluating oxidative status in these subjects. B vitamins (B(1), B(2), B(6), B(12), folate) in blood and plasma ghrelin level in these subjects were analyzed. Results showed that plasma level of ghrelin and lipid oxidation in NSCLC patients were significantly greater than control groups (P < 0.05). The activity of GPX, SOD, or catalase was significantly reduced, but XO activity was significantly elevated in NSCLC patients (P < 0.05). Plasma level of GSH was significantly lower, but GSSG level was significantly increased in NSCLC patients (P < 0.05). Vitamins B(2) and B(6) levels in red blood cells (RBC) from NSCLC patients were significantly lower (P < 0.05), and both were negatively correlated with plasma ghrelin. The correlation coefficients were -0.788 and -0.752, respectively. These data suggest that plasma GSH level may be a proper biomarker for evaluating oxidation status for NSCLC patients. RBC levels of vitamins B2 and B6 were reduced in NSCLC patients; thus, the importance of vitamins B(2) and B(6) for NSCLC patients could not be ignored.

Topics: Adult; Aged; Aged, 80 and over; alpha-Tocopherol; Ascorbic Acid; beta Carotene; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Catalase; Erythrocytes; Female; Ghrelin; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Health Status; Humans; Lipid Peroxidation; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Nutritional Status; Oxidation-Reduction; Oxidative Stress; Superoxide Dismutase; Vitamin B Complex; Xanthine Oxidase

Ascorbic acid (AA), the natural antioxidant, has been demonstrated to exert an antimetastatic action; however, AA is quite unstable in physiological condition. The aim of the present study is to investigate the stability, the antioxidation and the antimetastatic effects of three lipophilic AA derivatives in vitro as well as in vivo.. The 95D cells were treated with ascorbic acid-2-O-phosphate-6-O-laureate (AA2P6L), ascorbic acid-2-O-phosphate-6-O-myristate (AA2P6M) and ascorbic acid-2-O-phosphate-6-O-stearate (AA2P6S). AA derivatives' stability in medium under cell culture condition, in the presence and in the absence of 95D cells, was assessed by high-performance liquid chromatography assay. Cell viability and intracellular oxidative stress were measured by MTT assay and CDCFH assay, respectively. Wound healing assay and cell adhesion assay were used to investigate the antimetastatic activities against 95D cells in vitro, and the C57BL/6 mice model was used to evaluate the antimetastatic action in vivo.. All the three AA derivatives exhibited excellent stability, significantly different from AA. Results of MTT assay showed that IC(50) values of the cytotoxicity of those AA derivatives, namely AA2P6L, AA2P6M and AA2P6S, were 38.46, 28 and 22.97 microg/ml, while the CDCFH assay indicated that EC(50) values of antioxidant effects on 95D cells were 31.12, 33.51 and 38.31 microg/ml, respectively. Through the ratio of IC(50) vs EC(50) for AA derivatives, AA2P6L was demonstrated to be the most effective AA derivative, which retained the antioxidant ability as well as low cytotoxicity. AA2P6L dose-dependently inhibited 95D cells' migration and adhesion, by 50% at the concentration of 20 and 57 microg/ml, respectively. In the animal experiment, intraperitoneal administration of 75 mg/kg AA2P6L decreased the number of metastatic nodules by 62% and elevated the survival rate of C57BL/6 mice about onefold compared to the control group.. AA2P6L, a lipophilic AA derivative with antioxidation, is shown to be a potent antimetastatic agent through the inhibition of tumor invasion. These results support future investigations on the feasibility of cancer chemotherapy with AA2P6L.

Topics: Animals; Antioxidants; Ascorbic Acid; Cell Adhesion; Feasibility Studies; Injections, Intraperitoneal; Lung Neoplasms; Male; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Invasiveness; Tumor Cells, Cultured; Wound Healing

Interactions among beta-carotene (BC), alpha-tocopherol (AT) and ascorbic acid (AA) led to the hypothesis that using a combination of these antioxidants could be more beneficial than using a single antioxidant alone, particularly against smoke-related lung cancer. In this investigation, we have conducted an animal study to determine whether combined BC, AT and AA supplementation (AOX) protects against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis in smoke-exposed (SM) ferrets. Ferrets were treated for 6 months in the following four groups: (i) control, (ii) SM + NNK, (iii) AOX and (iv) SM + NNK + AOX. Results showed that the combined AOX supplementation (i) prevented the SM + NNK-decreased lung concentrations of retinoic acid (RA) and BC; (ii) inhibited the SM + NNK-induced phosphorylation of Jun N-terminal kinase (JNK), extracellular-signal-regulated protein kinase (ERK) and proliferating cellular nuclear antigen proteins in the lungs of ferrets; and (iii) blocked the SM + NNK-induced up-regulation of total p53 and Bax proteins, as well as phosphorylated p53 in the lungs of ferrets. In addition, there were no lesions observed in the lung tissue of ferrets in the control and/or the AOX groups after 6 months of intervention, but combined AOX supplementation resulted in a trend toward lower incidence of both preneoplastic lung lesions and lung tumor formation in SM + NNK + AOX group of ferrets, as compared with the SM + NNK group alone. These data indicate that combined AOX supplementation could be a useful chemopreventive strategy against lung carcinogenesis through maintaining normal tissue levels of RA and inhibiting the activation of mitogen-activated protein kinase pathways, cell proliferation and phosphorylation of p53.

Topics: alpha-Tocopherol; Animals; Antioxidants; Ascorbic Acid; bcl-2-Associated X Protein; beta Carotene; Blotting, Western; Carcinogens; Chromatography, High Pressure Liquid; Dietary Supplements; Enzyme Activation; Ferrets; Immunohistochemistry; JNK Mitogen-Activated Protein Kinases; Lung; Lung Neoplasms; Mitogen-Activated Protein Kinases; Nitrosamines; Proliferating Cell Nuclear Antigen; Tobacco Smoke Pollution; Tretinoin; Tumor Suppressor Protein p53

Ornithine decarboxylase (ODC) is a marker of lung cancer and is a key enzyme in the synthesis of polyamines, which are necessary for the promotion of the growth of malignant cells. This study assesses the dose-dependent effect of N-acetylcysteine (NAC), a chemopreventive agent, in combination with vitamin C (VC) on the activity of ODC in lung carcinoma cell line, NCI-H82. The cells were subjected to supplementation of NAC and VC both individually and in combination at different dosages for 24 h as well as 48 h. The cells were incubated with radiolabeled L-ornithine (14C) after the supplementation of NAC and VC individually as well as in combination. A microprocedure was carried out to estimate the activity of ODC in cells after 24 and 48 h of incubation. The activity which was found to be elevated in control cells was decreased significantly on drug supplementation in dose-dependent fashion. The content of nucleic acids also exhibited similar result and [3H]-thymidine incorporation was also affected by the supplementation.

Topics: Acetylcysteine; Ascorbic Acid; Cell Line, Tumor; Cell Proliferation; Cell Survival; DNA, Neoplasm; Dose-Response Relationship, Drug; Free Radical Scavengers; Humans; Lung Neoplasms; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; RNA, Neoplasm; Thymidine

Selenium, in the form of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) but not Se-enriched yeast (Se-yeast), was highly effective at inhibiting lung tumors induced by the tobacco specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mice and at reducing NNK-induced DNA methylation and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the lung. Our goal was to determine if p-XSC but not Se-yeast is effective at inducing levels of glutathione (GSH)-related antioxidants and reducing markers of GSH oxidation in the NNK-induced lung tumor model. In the first bioassay, 6-week-old mice were fed either control or experimental diets (containing 10 ppm as selenium from p-XSC or Se-yeast) and, beginning at 8 weeks of age, received NNK (3 micromol) by gavage once weekly for 8 weeks. After 18 weeks, p-XSC significantly reduced NNK-induced tumor burden by 74% (10.4 +/- 6.0 versus 2.7 +/- 1.5 tumors/mouse, P < 0.001) and tumor incidence from 96% to 68% (P < 0.01), whereas, Se-yeast had no effect. Lung GSH levels were unchanged by either NNK or Se-yeast, but were increased 70% in mice treated with both NNK and p-XSC (P < 0.01) and 41% in mice treated with p-XSC alone. In the second bioassay, the time course of effects of p-XSC was examined. As early as one week after initiation of p-XSC feeding lung and blood selenium levels were increased nearly six- and two-fold, respectively. Increases of 120% for GSH and 65% for Cys were observed in p-XSC groups compared to controls within one week after initiation of p-XSC feeding (P < 0.01). The levels of protein-bound:free GSH ratios and Cys ratios were significantly decreased in p-XSC-treated mice, regardless of NNK status, suggesting a decrease in the levels of oxidative stress. Altogether, these results indicate that p-XSC is a potent inducer of GSH and related thiol antioxidants in the lung leading to decreased levels of oxidative stress and suggest that p-XSC inhibits tumor formation, in part, by protecting against oxidative damage.

Topics: Animal Feed; Animals; Antioxidants; Ascorbic Acid; Cell Transformation, Neoplastic; Cysteine; Disulfides; Female; Glutathione; Lung Neoplasms; Mice; Molecular Structure; Nitrosamines; Organoselenium Compounds; Selenium; Sulfhydryl Compounds; Time Factors; Yeasts

The high incidence of lung cancer and ineffective toxic action of current mono and doublet chemotherapy approaches result in poor patient survival. Further, matrix metalloproteinases (MMPs) are implicated in neoplastic invasion and metastasis. Based on this, the authors investigated the effect of a dietary micronutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid, and green tea extract on the tumor growth of human lung carcinoma cell A-549 xenografts in athymic nude mice. Additionally, the authors tested the in vitro antitumor effect of NM on lung carcinoma A-549 cells by measuring cell proliferation by MTT assay, MMP-2 and -9 secretion by gelatinase zymography, and cell invasion through Matrigel. Nutrient supplementation strongly suppressed the growth of tumors without adverse effects in nude mice; tumor weight was reduced by 44% (P = .0001) and tumor burden was reduced by 47% (P < .0001) with supplementation. Zymography demonstrated in vitro secretion of MMP-2 by uninduced human lung carcinoma cells and both MMP-2 and -9 by phorbol 12-mysristate 13-acetate (PMA) (200 ng/mL)-treated cells. NM inhibited the secretion of both MMPs in a dose-dependent fashion, with virtual total inhibition at 500 microg/mL concentration. The invasion of human lung carcinoma cells through Matrigel was significantly reduced at 100 microg/mL (64%) and totally inhibited at 500 microg/mL concentration of NM (P = .01). Suppression of lung tumor growth in nude mice and inhibition of MMP secretion and Matrigel invasion suggest NM may act as an anticancer agent and as such warrants further investigation.

Topics: Adenocarcinoma; Animals; Antineoplastic Combined Chemotherapy Protocols; Ascorbic Acid; Camellia sinensis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Collagen; Dietary Supplements; Dose-Response Relationship, Drug; Drug Combinations; Drug Screening Assays, Antitumor; Humans; Laminin; Lung Neoplasms; Lysine; Mice; Mice, Nude; Plant Extracts; Proline; Proteoglycans

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

Redox-active iron present at physiological levels in the pulmonary epithelial lining fluid may lead to damage of lung tissue under some circumstances. For example, factors that increase potential for oxidative stress, such as higher intake of heme iron or higher intake of vitamin C in the presence of high intake of iron, might increase the risk of lung cancer, whereas higher intake of the antioxidant zinc might decrease that risk. During 16 yr of follow-up, 34,708 postmenopausal women, aged 55-69 yr at baseline who completed a food-frequency questionnaire for the Iowa Women's Health Study, were followed for 700 incident lung cancers. When subjects were stratified by intake of vitamin C supplements, among women who took vitamin C supplements of >500 mg/day, after adjusting for age, total energy intake, cigarette smoking, alcohol consumption, and dietary zinc or dietary heme iron intake, relative risks across categories of dietary heme iron intake were 1.0, 0.85, 0.93, 1.32, 1.70, and 3.77 (P for trend = 0.05; P for interaction = 0.08), whereas corresponding figures for dietary zinc intake were 1.0, 1.15, 0.71, 0.84, 0.61, and 0.11 (P for trend = 0.12; P for interaction = 0.04). The strength of the associations of heme iron and zinc intake with lung cancer appeared to be stronger with increasing levels of vitamin C supplement intake. Our results suggest that high dietary heme iron intake may increase the risk of lung cancer, whereas high dietary zinc may decrease the risk of lung cancer among postmenopausal women who consume high-dose vitamin C supplements. This finding may be of particular importance to smokers, for whom vitamin C supplementation is a common recommendation.

Topics: Aged; Antioxidants; Ascorbic Acid; Dietary Supplements; Dose-Response Relationship, Drug; Drug Interactions; Feeding Behavior; Female; Follow-Up Studies; Health Surveys; Heme; Humans; Iowa; Iron, Dietary; Lung Neoplasms; Middle Aged; Postmenopause; Risk Assessment; Risk Factors; Smoking; Women's Health; Zinc

Topics: Airway Obstruction; Antioxidants; Ascorbic Acid; Bronchoalveolar Lavage Fluid; Glutathione; Humans; Lung Neoplasms; Nitrites; Oxidative Stress; Proteins; Regression Analysis; Sputum; Uric Acid

Topics: Aged; Aged, 80 and over; Aging; Antioxidants; Ascorbic Acid; beta Carotene; Humans; Jaundice; Lung Neoplasms; Macular Degeneration; Middle Aged; Randomized Controlled Trials as Topic; Smoke Inhalation Injury; Vitamin E; Zinc

Animal studies have demonstrated that ozone exposure can induce lung tumors. Recent epidemiological studies have also shown that increased ozone exposure is associated with a greater risk of lung cancer. This study used single-cell gel electrophoresis (the Comet assay) and flow cytometry to investigate DNA damage in A549 cells exposed to ozone levels below the current ambient standard. Cells were exposed to ozone at levels of 0, 60, 80, and 120 ppb, and then DNA single-strand breaks and 8-oxoguanine levels were measured. Additionally, the formamidopyrimidine glycosylase (Fpg) repair enzyme was added to the Comet assay to enhance detection of oxidative damage. Vitamins C and E were also added to determine their inhibitory effects on ozone-induced 8-oxoguanine. Measurements of tail length, tail intensity, and tail moment of the Comet assay were shown to correlate with each other. However, tail moment appeared to be more sensitive than the other two indicators in detecting DNA single-strand breaks. Tail moments of cells exposed to 80 and 120 ppb of ozone were significantly higher than those exposed to 0 ppb (P<0.05). These three indicators of DNA single-strand breaks with Fpg were shown to be increased and more sensitive than those without Fpg. After Fpg was introduced, the tail moments at ozone levels of 60, 80, and 120 ppb were significantly higher than those at 0 ppb (P<0.05). Furthermore, 8-oxoguanine levels, determined by fluorescence intensity, at 80 and 120 ppb of ozone exposure were significantly higher than the level at 0 ppb. Pretreatment with vitamins C and E reduced the 8-oxoguanine levels caused by ozone. We conclude that ozone levels below current ambient standards may induce DNA breaks and oxidative DNA damage. Moreover, the Fpg repair enzyme in the Comet assay can increase the sensitivity of oxidative damage detection in vitro.

Topics: Antioxidants; Ascorbic Acid; Comet Assay; DNA Damage; DNA Repair; DNA-Formamidopyrimidine Glycosylase; Dose-Response Relationship, Drug; Guanine; Humans; Lung Neoplasms; Oxidants, Photochemical; Oxidative Stress; Ozone; Tumor Cells, Cultured; Vitamin E

Apurinic/apyrimidinic endonuclease is a key enzyme in the process of base excision repair, required for the repair of spontaneous base damage that arises as a result of oxidative damage to DNA. In mice, this endonuclease is coded by the Apex gene, disruption of which is incompatible with embryonic life. Here we confirm the embryonic lethality of Apex-null mice and report the phenotypic characterization of mice that are heterozygous mutants for the Apex gene (Apex+/-). We show that Apex heterozygous mutant cells and animals are abnormally sensitive to increased oxidative stress. Additionally, such animals manifest elevated levels of oxidative stress markers in serum, and we show that dietary supplementation with antioxidants restores these to normal levels. Apex+/- embryos and pups manifest reduced survival that can also be partially rescued by dietary supplementation with antioxidants. These results are consistent with a proposed role for this enzyme in protection against the deleterious effects of oxidative stress and raise the possibility that humans with heterozygous mutations in the homologous HAP1 gene may be at increased risk for the phenotypic consequences of oxidative stress in cells.

Topics: Adenocarcinoma, Papillary; Animals; Ascorbic Acid; Carbon-Oxygen Lyases; Cell Survival; Cells, Cultured; Dietary Supplements; Dinoprost; DNA-(Apurinic or Apyrimidinic Site) Lyase; Dose-Response Relationship, Drug; Embryo, Mammalian; Female; Fibroblasts; Genotype; Heterozygote; Lipid Peroxides; Lung Neoplasms; Lymphoma; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Mutant Strains; Oxidative Stress; Paraquat; Phenotype; Vitamin E; Vitamin K

We evaluated the association between exposure to environmental tobacco smoke (ETS) from husbands who smoke and plasma levels of antioxidant vitamins among nonsmoking women. A total of 1249 women from four areas in Italy answered a self-administered questionnaire, reported their diets on a food frequency questionnaire, had a medical examination, and gave their blood for alpha and beta-carotene, retinol, L-ascorbic acid, alpha-tocopherol, and lycopene determinations. Urinary cotinine was used to evaluate the level of recent exposure to ETS. After adjusting for study center, age and education, we found no association between ETS exposure and daily nutrient intake of beta-carotene, retinol, L-ascorbic acid, and alpha-tocopherol. However, we found an inverse dose-response relationship between intensity of current husband's smoke and concentrations of plasma beta-carotene and L-ascorbic acid. The associations remained even after controlling for daily beta-carotene and vitamin C intake and for other potential confounders (vitamin supplementation, alcohol consumption, and body mass index). Moreover, when urinary cotinine was considered as the exposure variable, a significant inverse association with plasma beta-carotene was found. The findings may be of interest to explain the biological mechanism that link ETS exposure with lung cancer and ischemic heart diseases.

Topics: Adult; Aged; Ascorbic Acid; beta Carotene; Cross-Sectional Studies; Environmental Exposure; Female; Humans; Lung Neoplasms; Male; Middle Aged; Myocardial Ischemia; Spouses; Tobacco Smoke Pollution

Binary systems combining a transition metal complex and ascorbate have been proposed recently for catalytic therapy of malignant tumors. The killing effect on tumor cells is achieved by production of free radicals in the course of accelerated oxidation of ascorbate by dioxygen in the presence of transition metal complexes. Further progress in the development of binary catalytic systems (BCSs) requires a special method for their investigation in cells and tissues, because neither component of BCSs fluoresces. Here a resonance Raman confocal spectral imaging (RR CSI) technique was introduced as a unique approach to monitor quantitatively the transition metal complexes within living cells. Intracellular accumulation, localization, and retention of theraphthal (TP), a catalyst of the advanced TP/ascorbate BCS, were investigated in A549 cells with the RR CSI technique. The cellular analysis was complemented with the detailed study of molecular interactions of TP in solution and environmental factors affecting the RR spectrum of TP. TP does not penetrate into membranes, it binds very weakly to DNA and RNA, but it readily forms complexes with proteins. Binding with Ca(2+) cations and decreasing pH below 6 induce aggregation of TP. By analyzing RR spectra recorded from every point within a TP-treated cell, three states of the agent were discriminated, namely, monomeric TP in polar environment, TP bound to proteins, and aggregated TP. Their cytoplasmic and nuclear distributions were mapped at different stages of uptake and efflux. By introducing organelle-selective fluorescent probes into drug-treated cells and measuring intracellular localization of both the probe and the drug, compartmentation of TP was revealed. Cell growth suppression by the TP/ascorbate system was measured, and probable molecular and organelle targets of radical damage were characterized.

Topics: Adenocarcinoma; Ascorbic Acid; Cell Division; Cell Survival; Humans; Indoles; Lung Neoplasms; Microscopy, Confocal; Spectrum Analysis, Raman; Tumor Cells, Cultured

Cigarette smokers are known to have lower concentrations of circulating ascorbic acid than nonsmokers. In contrast, there is evidence that the extracellular fluid lining of the alveolus, which comes in close contact with cigarette smoke, and the alveolar macrophages of smokers are enriched with ascorbic acid. The clinical significance of these observations is unknown.. The authors measured the ascorbic acid concentrations and radiolabeled methyl incorporation (which is inversely related to the degree of DNA methylation in vivo) of paired samples of squamous cell carcinoma (SCC) and adjacent uninvolved mucosa of the lung and larynx (n = 22).. Cancerous tissues had significantly higher ascorbic acid concentrations (mean +/- standard deviation [SD, 485 +/- 77; median, 483 ng/mg protein) compared with their matched uninvolved tissues (mean +/- SD, 151 +/- 52; median, 72 ng/mg protein; P < 0.0001). The radiolabeled methyl incorporation was significantly higher in cancerous tissues (mean +/- SD, 31,419 +/- 2629; median, 31,416 counts per minute [CPM]/microg DNA) compared with their matched uninvolved tissues (mean +/- SD, 11,883 +/- 1567; median, 11,444 CPM/microg DNA; P < 0.0001). The Spearman correlation between ascorbic acid concentrations and radiolabeled methyl incorporation by DNA in SCCs was inverse and statistically significant (r = -0.58, P = 0.008), indicating a beneficial effect of accumulated ascorbic acid in global methylation of DNA. In the uninvolved tissues, this correlation was inverse but statistically not significant (r = -0.20, P =0.35).. Cancerous tissues of the lung and larynx demonstrated their ability to accumulate ascorbic acid. The accumulation of ascorbic acid by these tissues seemed to facilitate global methylation of DNA.

Topics: Aged; Aged, 80 and over; Ascorbic Acid; Carcinoma, Squamous Cell; DNA Methylation; Female; Humans; Laryngeal Neoplasms; Lung Neoplasms; Male; Middle Aged; Smoking

Both ascorbic acid (AsA, vitamin C) and N-acetylcysteine (NAC), a precursor and analogue of glutathione, possess a broad array of biological properties underlying their protective role in a variety of pathophysiological conditions. However, under certain circumstances, AsA behaves as a pro-oxidant rather than an anti-oxidant and produces adverse effects. This prompted us to evaluate whether NAC could interact with AsA in preventing mutation and cancer. AsA significantly increased spontaneous revertants in the Salmonella typhimurium strains TA102 and TA104, which are sensitive to oxidative mutagens. In contrast, NAC lowered the spontaneous background in TA104 and neutralized the negative effects of AsA. Moreover, NAC and AsA showed additive effects in reducing chromium(VI) and in reverting its mutagenicity. A single i.p. injection of urethane (1 g/kg body weight) to 120 A/J mice resulted, after 4 months, in the formation of a total of 1,532 lung tumors, 425 in the 30 mice treated with the carcinogen only, 404 in those treated with urethane plus AsA, 365 in those treated with urethane plus NAC and 338 in those treated with urethane plus the combination of AsA and NAC (both given daily with drinking water at the dose of 1 g/kg body weight). Compared to positive controls, tumor multiplicity was poorly affected by AsA, whereas it was significantly decreased by NAC and even more so by its combination with AsA. The overall volumes of lung tumors in the 4 groups were 107.5, 89.3, 61.3 and 49.7 mm(3), respectively. Tumor sizes were slightly but significantly decreased in mice treated with AsA and more so in those treated with NAC and NAC plus AsA, their combination being significantly more effective than each individually. All protective effects elicited by combining the 2 drugs were additive. Therefore, NAC prevents the adverse effects of AsA on spontaneous mutagenicity; at the same time, this thiol behaves in an additive fashion with AsA, inhibiting the mutagenicity of chromium(VI) and the lung tumorigenicity of urethane in mice. These findings suggest that NAC and AsA could conveniently be combined in cancer chemoprevention and other pharmacological interventions.

Topics: Acetylcysteine; Animals; Ascorbic Acid; Carcinogenicity Tests; Cell Transformation, Neoplastic; Chromium; Drug Stability; Female; Lung Neoplasms; Mice; Mutagenesis; Urethane

Cyclin D1 antisense (D1AS)-transfected lung epithelial cell lines were serum deprived and then analyzed for three hallmarks of apoptosis: appearance of single-strand DNA breaks, alteration of apoptosis-related protein expression, and induction of chromatin condensation. Single-strand DNA breaks appeared at significant levels 24 h after serum deprivation, whereas induction of chromatin condensation was observed after 72 h. The antioxidants dimethyl sulfoxide, ascorbate, and glutathione, as well as insulin-like growth factor-I, inhibited induction of DNA damage in this assay. Additionally, proliferating cell nuclear antigen expression is completely suppressed in the D1AS cells, indicating a mechanism to explain the reduced capacity for DNA repair. Increased expression of cyclin D1, which is a common lesion in lung cancer, may thus prevent induction of apoptosis in an oxidizing and growth factor-poor environment. Reducing cyclin D1 expression in lung cancer cells by expression of D1AS RNA disrupted these protective pathways.

Topics: Antioxidants; Apoptosis; Ascorbic Acid; Culture Media, Serum-Free; Cyclin D1; Dimethyl Sulfoxide; DNA Damage; DNA Repair; Gene Expression Regulation, Neoplastic; Glutathione; Humans; Insulin-Like Growth Factor I; Lung Neoplasms; Oligodeoxyribonucleotides, Antisense; Proliferating Cell Nuclear Antigen; Tumor Cells, Cultured

To study any possible association between serum ascorbic acid and uric acid levels with lung cancer.. Serum ascorbic acid and uric acid levels in lung cancer patients (n = 30) and healthy controls (n = 45) were measured.. The mean values for serum ascorbic acid were found to be significantly lower (P< 0.05) in patients (0.112+/-0.020) than in controls (0.394+/-0.029). Serum uric acid levels of patients were also significantly lower than those of controls (P< 0.05).. There was no association between serum levels of ascorbic acid and uric acid, cholesterol, triglyceride and albumin levels with lung cancer.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Cholesterol; Female; Humans; Lung Neoplasms; Male; Middle Aged; Serum Albumin; Triglycerides; Uric Acid

The induction of apoptosis by the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) has been documented in vitro in various cancer types. A role for reactive oxygen species (ROS) in apoptosis induced by 4HPR in some cancer cells has been demonstrated recently. We studied five different human head and neck and five lung cancer cell lines to determine whether the ROS play a general role in 4HPR-induced apoptosis. We found that 4HPR induced apoptosis in all of the cell lines; however, this effect was blocked by antioxidants in only 2 of the 10 cell lines. 4HPR induced a greater than 4-fold increase in the generation of intracellular ROS in these two cell lines compared with a much lower effect in other cell lines. Furthermore, these two cell lines were most sensitive to the induction of apoptosis by 4HPR. The level of the cellular antioxidant thiol and superoxide dismutase activity were relatively lower in cells, which responded to 4HPR with a high level of ROS generation. These results indicate that although ROS can mediate 4HPR-induced apoptosis in some cells, which may have a low endogenous cellular antioxidant levels, other mechanisms exist for 4HPR-induced apoptosis. One such mechanism may involve retinoic acid receptors (RARs) because an RAR antagonist was able to block partially 4HPR-induced apoptosis. In conclusion, 4HPR-induced apoptosis involves at least three different mechanisms, which are complex and can overlap in the same cell line: (a) one mechanism involving 4HPR-induced ROS; (b) one involving RARs; and (c) at least one that does not involve ROS or RARs and remains unclear.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Ascorbic Acid; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Fenretinide; Head and Neck Neoplasms; Humans; Lung Neoplasms; Naphthalenes; Neoplasm Proteins; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Receptors, Retinoic Acid; Sulfhydryl Compounds; Superoxide Dismutase; Tumor Cells, Cultured

A lipophilic and auto-oxidation-resistant derivative of ascorbic acid (Asc), Asc-2-O-phosphate-6-O-palmitate (Asc2P6Plm), was shown to exert an invasion-inhibitory action as promptly as 30-40 min for 50% inhibition and 60-90 min for 80% inhibition after entering fibrosarcoma HT-1080 cells. Invasive inhibition of 95-97% was accomplished by Asc2P6Plm of doses exhibiting no cytotoxicity under the same conditions. Asc2P6Plm was dephosphorylated and esterolyzed to Asc, which enriched the intracellular Asc dose dependently in invasion-suppressed cells, contrasting with no detectable Asc in invasive cells fed without Asc2P6Plm. Intracellular dehydroAsc (DehAsc), unexpectedly, amounted to 1.02-1.65-fold as much as intracellular Asc, suggesting that invasive cells underwent oxidative stress, the repression of which resulted in both inhibition of tumor invasion and oxidative conversion of Asc to DehAsc. Correspondingly, intracellular oxidants fluorometrically detected with a redox indicator CDCFH were more abundant in invasive cells than in invasion-suppressed cells fed with Asc2P6Plm. Invasion inhibitory effects of Asc2P6Plm necessitated the extensive inhibition of the major gelatinases MMP-9 and MMP-2, as shown by zymography and Western blots, but did not necessitate direct expression of the metastasis suppressor gene nm23, taking as long as 6-18 h in contrast to a prompt action of Asc2P6Plm. Antimetastatic effects on melanoma B16BL6 cells were given dose dependently by intravenous administration or pretreatment with Asc2P6Plm. Thus, Asc2P6Plm is anticipated as an antimetastatic agent via the potent antioxidant activity.

Topics: Animals; Antineoplastic Agents; Antioxidants; Ascorbic Acid; Cell Survival; Dose-Response Relationship, Drug; Female; Humans; Immunohistochemistry; Lung Neoplasms; Matrix Metalloproteinases; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Transplantation; Oxidative Stress; Reactive Oxygen Species; Time Factors; Tumor Cells, Cultured

Topics: Adenocarcinoma; Ascorbic Acid; Ascorbic Acid Deficiency; Gingivitis; Humans; Lung Neoplasms; Male; Middle Aged; Polycythemia Vera; Scurvy

Lung cancers occur more commonly in the upper lobes than in the lower lobes, but its pathophysiologic basis is not well understood. Because numerous studies have reported a consistent inverse relationship between lung cancer risk and intake of certain vegetables and fruits, we hypothesized that the balance between diet-derived protective substances delivered via the circulation and cigarette-derived carcinogenic substances delivered via the airways would be less favorable in the upper lobes compared with the lower lobes, hence accounting for the upper lobe predominance of tumors among smokers. Thus, we examined the association between diet and tumor location in 328 patients with lung cancer. The ratio of upper to lower lobe tumors was 2.5:1.0. In univariate analysis, age, height, weight, sex, race, family history of cancer, education level, tumor histology, calories consumed per day, and intake of animal fat did not differ significantly between patients with upper versus lower lobe tumors. Predictors of tumor location in univariate analysis were family history of lung cancer; smoking history; history of asbestos exposure; and intakes of yellow-orange vegetables, alpha-carotene, beta-carotene, and vitamins A, C, and E. In multivariable logistic regression analysis, the independent predictors of upper lobe tumor location were family history of lung cancer (p = 0.03), history of asbestos exposure (p = 0.02), less intake of yellow-orange vegetables (p < 0.04), and less intake of vitamin E (p = 0.05). Our results show a strong inverse association between upper lobe location of lung cancer and intake of yellow-orange vegetables and vitamin E.

Topics: Administration, Inhalation; Age Factors; Aged; Analysis of Variance; Anticarcinogenic Agents; Antioxidants; Asbestos; Ascorbic Acid; beta Carotene; Carcinogens; Carotenoids; Diet; Dietary Fats; Educational Status; Energy Intake; Female; Forecasting; Fruit; Humans; Logistic Models; Lung; Lung Neoplasms; Male; Racial Groups; Risk Factors; Sex Factors; Smoking; Vegetables; Vitamin A; Vitamin E

The authors studied the intake of vegetables, fruits, beta-carotene, and vitamins C and E in relation to the incidence of lung cancer. For 561 men from the town of Zutphen, the Netherlands, dietary history information was obtained in 1960, 1965, and 1970. During 1971-1990, 54 new cases of lung cancer were identified. The data were analyzed using Cox proportional hazard analyses, adjusting for age, pack-years of cigarettes, and energy intake. No relation between intake of vitamin E and lung cancer risk was seen. For vitamin C intake, the results pointed to an inverse association, although not entirely consistently. Furthermore, it was observed that participants with low stable intakes (i.e., low in 1960, 1965, and 1970) of vegetables, fruits, and beta-carotene experienced more than twofold increased relative risks of lung cancer than those with high stable intakes. For participants with low average intakes, relative risks were much lower and not statistically significant. The authors conclude that there is no apparent relation of vitamin E to lung cancer risk; however, for beta-carotene, vitamin C, vegetables, and fruit, most studies, including the present one, suggest weak inverse associations. The use of repeated intake measurements to select subgroups with stable, highly contrasting intakes may be a promising approach for studying diet-cancer relations.

Topics: Ascorbic Acid; beta Carotene; Diet; Diet Surveys; Follow-Up Studies; Fruit; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Netherlands; Proportional Hazards Models; Risk; Vegetables; Vitamin E

Increasing evidence suggests that cancer patients express oxidative disturbances. The main objective of this cross-sectional case-control study (n = 57 + 76) was to explore whether lung cancer patients, when compared to healthy controls, have alterations in their plasma peroxyl radical trapping capacity (TRAP). Group matching was used with respect to age, sex and smoking history. A secondary objective was to observe the effects of life-long cigarette consumption on plasma TRAP and its components. Mean TRAP values were significantly lower in the cancer patients than in the control group (1143 vs 1273 mumol/l, p = 0.0002). Moreover, all the components of TRAP (except uric acid) were significantly lower in the cancer group: protein SH-groups 442 vs 571 mumol/l, ascorbic acid 34.0 vs 46.5 mumol/l and vitamin E 25.0 vs 33.8 mumol/l. The as yet unidentified antioxidant compounds in plasma contributed 26.5% of plasma TRAP in the cancer group and 30.2% in the control group. There was no correlation between cigarette consumption in pack-years and plasma TRAP; however, plasma concentrations of uric acid and ascorbic acid were negatively correlated with cigarette consumption.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Ascorbic Acid; Case-Control Studies; Cholesterol; Cross-Sectional Studies; Female; Free Radicals; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxidative Stress; Peroxides; Smoking; Weight Loss

The relation between the dietary intake of vitamins E, C, and A (estimated by a 24-hour recall) and lung cancer incidence was examined in the First National Health and Nutrition Examination Survey Epidemiologic Followup Study cohort of 3,968 men and 6,100 women, aged 25-74 years. During a median follow-up period of 19 years (from 1971-1975 to 1992), 248 persons developed lung cancer. Adjusted for potential confounders using Cox proportional hazards regression methods with age as the underlying time variable, the relative risk of lung cancer for subjects in the highest quartile of vitamin C intake compared with those in the lowest quartile was 0.66 (95% confidence interval (CI) 0.45-0.96). For vitamin A intake, a protective effect was observed only for its fruit and vegetable component (carotenoids) among current smokers (relative risk = 0.49, 95% CI 0.29-0.84), but this was modified by the intensity of smoking (a statistically significant effect (relative risk = 0.33, 95% CI 0.13-0.84) was observed only for those in the lowest tertile of pack-years of smoking). The vitamin E intake-lung cancer relation was modified by the intensity of smoking with a significant protective effect confined to current smokers in the lowest tertile of pack-years of smoking (relative risk = 0.36, 95% CI 0.16-0.83). Overall, there was no additional protective effect of supplements of vitamins E, C, and A beyond that provided through dietary intake. When vitamin E, vitamin C, and carotenoid intakes were examined in combination, a strong protective effect was observed for those in the highest compared with those in the lowest quartile of all three intakes (relative risk = 0.32, 95% CI 0.14-0.74). These data provide support for a protective role of dietary vitamins E and C and of carotenoids against lung cancer risk but with a modification in effects by the intensity of cigarette exposure. While smoking avoidance is the most important behavior to reduce lung cancer risk, the daily consumption of a variety of fruits and vegetables that provides a combination of these nutrients and other potential protective factors may offer the best dietary protection against lung cancer.

Topics: Adult; Aged; Alcohol Drinking; Ascorbic Acid; Carotenoids; Female; Follow-Up Studies; Fruit; Humans; Lung Neoplasms; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Smoking; Vegetables; Vitamin A; Vitamin E

Lung cancer cases diagnosed during the period 1975 through 1993 and matched controls were identified in the rosters of Washington County, Maryland residents who had donated blood for a serum bank in 1974 or 1989. Plasma from participants in the 1989 project was assayed for ascorbic acid; serum or plasma was assayed for participants in either project for alpha- and beta-carotene, cryptoxanthin, lutein/zeaxanthin, lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Among the total group of 258 cases and 515 controls, serum/plasma concentrations were significantly lower among cases than controls for cryptoxanthin, beta-carotene, and lutein/zeaxanthin with case-control differences of -25.5, -17.1, and -10.1%, respectively. Modest nonsignificant case-control differences in a protective direction were noted for alpha-carotene and ascorbic acid. There were only trivial differences for lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity. Findings are reported for males and females and for persons who had never smoked cigarettes, former smokers, and current smokers at baseline. These results and those from previous studies suggest that beta-carotene is a marker for some protective factor(s) against lung cancer; that cryptoxanthin, alpha-carotene, and ascorbic acid need to be investigated further as potentially protective factors or associates of a protective factor; and that lycopene, alpha-tocopherol, selenium, and peroxyl radical absorption capacity are unlikely to be associated with lung cancer risk. Until specific preventive factors are identified, the best protection against lung cancer is still the avoidance of airborne carcinogens, especially tobacco smoke; second best is the consumption of a diet rich in fruits and vegetables.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Biomarkers; Carotenoids; Case-Control Studies; Female; Free Radicals; Humans; Linear Models; Lung Neoplasms; Male; Middle Aged; Oxidation-Reduction; Risk Factors; Selenium; Smoking; Tobacco Smoke Pollution; Vitamin E

Ascorbic acid and its salts (AA) are preferentially toxic to tumor cells in vitro and in vivo. Given in high enough doses to maintain plasma concentrations above levels that have been shown to be toxic to tumor cells in vitro, AA has the potential to selectively kill tumor cells in a manner similar to other tumor cytotoxic chemotherapeutic agents. Most studies of AA and cancer to date have not utilized high enough doses of AA to maintain tumor cytotoxic plasma concentrations of AA. Data are presented which demonstrate the ability to sustain plasma levels of AA in humans above levels which are toxic to tumor cells in vitro and suggests the feasibility of using AA as a cytotoxic chemotherapeutic agent.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Cell Line; Cell Survival; Humans; Infusions, Intravenous; Lung Neoplasms; Mice; Neoplasms; Tumor Cells, Cultured

To evaluate if there are differences in lung cancer incidence between socioeconomic groups in the Netherlands and if so, if smoking habits and other lifestyle characteristics could explain these differences.. Prospective cohort study. Baseline measurement included information on socioeconomic status, smoking habits, and other covariates by means of a self-administered questionnaire. Follow up was established by computerised record linkage to cancer registries and a pathology register.. Population originating from 204 municipalities in The Netherlands.. 58,279 men aged 55-69 years in September 1986. After 3.3 years of follow up 490 microscopically confirmed incident lung cancer cases were detected.. An inverse association between lung cancer risk and highest level of education was found, which persisted after adjustment for age, smoking, dietary intake of vitamin C, beta-carotene and retinol (rate ratio (RR) highest/lowest level of education = 0.52, 95% CI 0.33, 0.82, trend p < 0.001). Men with a lower white collar profession had a significantly lower relative rate of lung cancer compared with blue collar workers (RR = 0.66, 95% CI 0.47, 0.96), but after adjustment for smoking habits this difference was reduced (RR = 0.73, 95% CI 0.51, 1.08).. There is an inverse association between highest level of education and lung cancer, which is still apparent after adjustment for age, smoking, dietary intake of vitamin C, beta-carotene and retinol. The significantly lower lung cancer risk of lower white collar workers compared with the risk of blue collar workers could be partially explained by smoking habits.

Topics: Age Factors; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Cohort Studies; Diet; Educational Status; Follow-Up Studies; Humans; Incidence; Life Style; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Netherlands; Prospective Studies; Risk Factors; Smoking; Social Class; Socioeconomic Factors

A human cell subline (PC-9/VCR) resistant to vincristine was established from non-small cell lung cancer PC-9 cells by incremental exposure of the cells to vincristine. The resistant cells showed phenotypic resistance to vincristine (10-fold), colchicine (6.9-fold) and cisplatin (1.4-fold) but they showed sensitivity to other chemotherapeutic agents including melphalan and etoposide VP-16. The characteristics of the vincristine resistance was partially inhibited (5-7-fold) by co-treatment of PC-9/VCR cells with a nontoxic concentration of L-ascorbic acid (25 micrograms/ml). Co-treatment or 96 h pre-treatment with ascorbic acid resulted in potentiation of the vincristine effect on the resistant, but not on the sensitive, cell line. The growth inhibition due to vincristine treatment after 24 or 96 h growth in ascorbic acid-free medium was decreased in the resistant as well as in the sensitive cell line. In both cell lines, enhanced growth rate has been shown after ascorbic acid treatment. Similarly, cross-resistance of PC-9/VCR cells to colchicine could also be blocked by ascorbic acid. In addition, a nontoxic concentration of verapamil, a known multidrug resistance inhibitor, did not affect the resistant phenotype of PC-9/VCR cells. These findings suggest that an ascorbic acid-sensitive mechanism may be involved in drug resistance per se in the human lung cancer cells, which differs from the classical phosphoglycoprotein-mediated or previously reported non-phosphoglycoprotein-mediated multidrug resistance.

Topics: Ascorbic Acid; Carcinoma, Non-Small-Cell Lung; Cell Division; Culture Media; Drug Resistance; Drug Synergism; Humans; Lung Neoplasms; Tumor Cells, Cultured; Verapamil; Vincristine

A human lung-cancer PC-9 subline with acquired resistance to vincristine (VCR), a chemotherapeutic agent, was established with incremental increases of the drug. The resistant PC-9 subline (PC-9/VCR) shows a 12-fold increase in resistance to VCR and a unique cross-resistance pattern: high cross-resistance to the potent VCR analogue colchicine (6.9-fold) and vinblastine (2.5-fold); lower cross-resistance to actinomycin D (1.8-fold), cisplatin (1.2-fold) and adriamycin (1.3-fold) and a sensitivity to melphalan and VP-16 which is similar to that of the parental cell line. A reduced accumulation of VCR in the resistant cells was demonstrated. Interestingly, the VCR resistance of the PC-9/VCR cell line was partially reversed by ascorbic acid, and the drug uptake was enhanced. In contrast, ascorbic acid had no effect on drug tolerance and drug accumulation was not observed in either PC-9 parental cells or known multidrug-resistant (MDR) cells, suggesting that VCR resistance in PC-9/VCR cells results essentially from reduced drug accumulation. It is worth noting that, whereas reduced drug accumulation in the PC-9/VCR cells was susceptible to modulation by ascorbic acid, the increased efflux rate characteristic of the resistant cells was not. Further, there was a higher efflux rate in resistant cells than in parental cells. DNA Southern- and RNA Northern-blot hybridization analyses indicate that PC-9/VCR cells do not contain amplified mdr genes or overexpress P-glycoprotein. In addition, the calcium-channel blocker verapamil, which acts as a competitive inhibitor of drug binding and efflux, did not affect the resistant phenotype of PC-9/VCR cells. These findings suggest an ascorbic acid-sensitive drug uptake mechanism which is important in mediating VCR resistance per se in human lung-cancer cells; this differs from the P-glycoprotein-mediated MDR mechanism.

Topics: Ascorbic Acid; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinoma, Non-Small-Cell Lung; Carrier Proteins; Cisplatin; Colchicine; Dactinomycin; Doxorubicin; Drug Resistance; Gene Expression; Humans; Lung Neoplasms; Membrane Glycoproteins; Tumor Cells, Cultured; Vinblastine; Vincristine

Topics: Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Humans; Lung Neoplasms; Smoking; Vitamin E

The effect of ascorbic acid 6-docosahexaenoate (DHA-VC) on the phospholipase-C-mediated hydrolysis of phosphatidylcholine was investigated. In human non-small cell lung cancer cells (PC-14) exposed to DHA-VC for 24 hr, a dose-dependent increase in phosphatidylcholine-specific phospholipase C (PC-PLC) activity was seen. PC-PLC activity in whole-cell homogenate of PC-14 cells was increased about 2.5-fold by 2 hr of treatment with DHA-VC (20 micrograms/ml). Treatment with DHA-VC also augmented PC-PLC activity in the crude membrane extract. On the other hand, DHA-VC inhibited the activity of phospholipase A2 (ID50 = 800 micrograms/ml). Another water-soluble analog, choline docosahexaenoate, also stimulated PC-PLC activity. To explore the effect of DHA-VC on phosphatidylcholine turnover, we analyzed phospholipids labeled with [14C] choline or [3H]myristate by thin-layer chromatography, and found that the amount of [14C]- and [3H]-labeled phosphatidylcholine was constant in the presence of DHA-VC. These results suggest that phosphatidylcholine turnover was not influenced by DHA-VC. DHA-VC treatment increased protein kinase C activity of the cells in the late phase (120 min), suggesting that DHA-VC-induced diacylglycerol production mediated by PC-PLC causes protein kinase C activation. Considering that significant inhibition of DNA synthesis occurred 12 hr after 2 hr of treatment with DHA-VC (20 micrograms/ml), DHA-VC-induced PC-PLC activation seems to be an early event in DHA-VC-induced cytotoxicity, which suggests that the effects of DHA-VC on signal transduction pathways may play an important role in the cytotoxicity of DHA-VC.

Topics: Ascorbic Acid; Carcinoma, Non-Small-Cell Lung; Choline; Diglycerides; DNA; Docosahexaenoic Acids; Humans; Lung Neoplasms; Phosphatidylcholines; Phospholipases A; Phospholipases A2; Solubility; Tumor Cells, Cultured; Type C Phospholipases; Water

Selenium has been suggested to be anticarcinogenic and to play a role in the cellular defense against oxidative stress. The association between toenail selenium (a marker of long-term selenium status) and lung cancer was investigated in a cohort study of diet and cancer that started in 1986 among 120,852 Dutch men and women aged 55-69 years. After 3.3 years of follow-up, 550 incident cases of lung carcinoma were detected. Toenail selenium data were available for 370 lung cancer cases and 2459 members of a randomly selected subcohort. The rate ratio of lung cancer for subjects in the highest compared to the lowest quintile of toenail selenium, after controlling for age, gender, smoking, and education, was 0.50 (95% confidence interval, 0.30-0.81), with a significant inverse trend across quintiles (P = 0.006). The protective effect of selenium was concentrated in subjects with a relatively low dietary intake of beta-carotene or vitamin C. The rate ratio in the highest compared to the lowest quintile of selenium was 0.45 in the low beta-carotene group (95% confidence interval, 0.22-0.92; trend P = 0.028) and 0.36 in the low vitamin C group (95% confidence interval, 0.17-0.75; trend P < 0.001). The results of this study support an inverse association between selenium status and lung cancer and suggest a modification of the effect of selenium by the antioxidants beta-carotene and vitamin C.

Topics: Adenocarcinoma; Age Factors; Aged; Ascorbic Acid; beta Carotene; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Carotenoids; Cohort Studies; Education; Feeding Behavior; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Nails; Netherlands; Prospective Studies; Risk Factors; Selenium; Sex Factors; Smoking; Surveys and Questionnaires; Time Factors; Toes; Vitamin A

Six synthetic 2,6-dimethoxyhydroquinone derivatives were shown to have different degrees of cytotoxicity to two human tumor cell lines (KB and PC-9) under the synergistic activation of L-ascorbic acid. Two representative compounds displayed very low time-schedule-independent index, showing that the cytotoxic action is independent of time of drug treatment. The addition of catalase produced a significant inhibitory effect on the cytotoxicity of two representative compounds, indicating that the cytotoxic action is mediated by the generation of H2O2, which may yield hydroxyl radicals via various mechanisms. ESR studies employing the spin-trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) showed that massive hydroxyl radicals were generated from four of these drugs as a non-linear function of L-ascorbic acid concentration. The results indicate the possible involvement of hydroxyl radicals in the cytotoxic action of these novel drugs.

Topics: Adenocarcinoma; Aminacrine; Antineoplastic Agents; Ascorbic Acid; Carcinoma, Squamous Cell; Catalase; Drug Interactions; Electron Spin Resonance Spectroscopy; Humans; Hydroquinones; Hydroxides; Hydroxyl Radical; Lung Neoplasms; Mouth Neoplasms; Time Factors; Tumor Cells, Cultured

In the first part of this study we have shown how the serum levels of four selected tumour markers, namely tissue polypeptide antigen (TPA), carcino-embryonic antigen (CEA), hyaluronic acid (HA) and ferritin, display patterns characteristic of mesothelioma (M) or bronchogenic carcinoma (BC) in asbestos-exposed workers, and we hypothesize that the differences in marker patterns correspond to differences in carcinogenesis mechanisms. In a preliminary study, we found these specific marker patterns in 5/19 exposed workers of whom only one demonstrated any radiological signs of disease. Thus these specific marker patterns may be early events, occurring long (possibly years) before the classical radiological signs of exposure to asbestos. Accordingly they afford an optimal opportunity for prevention which should be adapted to the carcinogenesis mechanism as it is revealed by the marker pattern; it is aimed at antagonizing free radical carcinogenesis in all persons with TPA levels in excess of 100 U/l or Ferritin in excess of 400 ng/ml, and at inhibiting chemical carcinogenesis in those having elevated CEA levels (over 3 ng/ml). The mechanisms involved in these inhibitory processes are described and discussed, as well as the practical implementations that proceed from them. A prevention trial is now being started among 300 active and retired workers of an asbestos-cement works in northern France; the design of the study is presented. This prevention programme should be maintained over many years and holds a strong potential for reducing the untoward effects of exposure to asbestos.

Topics: Acetylcysteine; Antigens, Neoplasm; Asbestos; Ascorbic Acid; beta Carotene; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Bronchogenic; Carotenoids; Cohort Studies; Ferritins; Humans; Hyaluronic Acid; Longitudinal Studies; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Occupational Diseases; Occupational Exposure; Peptides; Riboflavin; Selenium; Tissue Polypeptide Antigen; Vitamin A; Vitamin E

In 1966, a cohort of White males aged 35 or over, who were policy-holders with the Lutheran Brotherhood Insurance Society (United States), completed a mail questionnaire on tobacco use, diet, and demographic characteristics. During the 20 years of follow-up, 219 lung cancer deaths occurred. Besides the strong relationship with cigarette smoking, we observed an effect on lung cancer risk among current users of cigars or pipes who were nonsmokers of cigarettes (relative risk [RR] = 3.5, 95 percent confidence interval [CI] = 1.0-12.6) or who were past/occasional users of cigarettes (RR = 2.7, CI = 1.4-5.3). In addition, elevated risks (from 1.5 to 2.6) of lung cancer were found among craftsmen and laborers, with the highest risks among subjects who worked in the mining or manufacturing industry. No association between current (as of 1966) use of beer or hard liquor and lung cancer was observed, although past users were at elevated risk. An inverse association between lung cancer and intake of fruits was observed, and risks of lung cancer were lower among persons in the highest dietary intake quintiles of vitamins A and C. Except for oranges, however, none of the inverse associations with fruits or dietary nutrients had statistically significant trends. The findings from this cohort study add to the evidence of an adverse effect of cigar/pipe smoking and possibly protective effect of dietary factors on lung cancer risk.

Topics: Ascorbic Acid; Diet; Follow-Up Studies; Humans; Insurance, Life; Lung Neoplasms; Male; Nutrition Surveys; Occupations; Risk Factors; Smoking; Surveys and Questionnaires; United States; Vitamin A; White People

Vitamins A, C, D, (VA, VC, VE) and carotene (CAR) in plasma and riboflavin (VB2) in urine samples were measured to evaluate the nutritional status of 44 non-mining workers, 81 miners and 43 lung cancer patients in Yunnan Tin Mine. Plasma VA in these 3 groups averaged 46.6, 52.8, and 47.8 micrograms/dl, respectively, with 0, 0 and 7.2% of the individuals having levels under 20 micrograms/dl. The average levels of plasma CAR among these 3 groups were 153.6, 123.0 and 137.1 micrograms/dl. CAR contents in miners were significantly lower (P less than 0.01) than those of non-mining workers. About 1/4 of the miners and 1/6 of the lung cancer patients had values less than 80 micrograms/dl. Plasma VC among these 3 groups averaged 423, 406 and 360 micrograms/dl, respectively, with 14.0, 11.5 and 25.6% of the individuals having levels under 300 micrograms/dl. The average plasma VE contents ranged from 648.3 to 722.0 micrograms/dl for the 3 groups. 70.5% of non-mining workers. 42.0% of miners and 39.5% of the lung cancer patients had levels less than 700 micrograms/dl, which is considered either low or deficient in nutritional surveys. 52.3% of the non-mining workers and 51.8% of the miners were either low or deficient in VB2. Although there was intermittent supplementation of riboflavin in lung cancer patients, the low and deficient VB2 nutritional status was still observed in 27.9% of them. The study establishes the low nutritional status in vitamins of the high lung cancer risk population in Yunnan Tin Mine and provides a background for a nutritional intervention trial to prevent lung cancer in the miners.

Topics: Ascorbic Acid; Carotenoids; Humans; Lung Neoplasms; Male; Mining; Riboflavin; Risk; Tin; Vitamin A; Vitamin E; Vitamins

The relation between the intake of retinoids, carotenoids, vitamin E, vitamin C, and selenium and the subsequent risk of lung cancer was studied among 4,538 initially cancer-free Finnish men aged 20-69 years. During a follow-up of 20 years beginning in 1966-1972, 117 lung cancer cases were diagnosed. Inverse gradients were observed between the intake of carotenoids, vitamin E, and vitamin C and the incidence of lung cancer among nonsmokers, for whom the age-adjusted relative risks of lung cancer in the lowest tertile of intake compared with that in the highest tertile were 2.5 (p value for trend = 0.04), 3.1 (p = 0.12), and 3.1 (p less than 0.01) for the three intakes, respectively. Adjustment for various potential confounding factors did not materially alter the results, and the associations did not seem to be due to preclinical cancer. In the total cohort, there was an inverse association between intake of margarine and fruits and risk of lung cancer. The relative risk of lung cancer for the lowest compared with the highest tertile of margarine intake was 4.0 (p less than 0.001), and that for fruits was 1.8 (p = 0.01). These associations persisted after adjustment for the micronutrient intakes and were stronger among nonsmokers. The results suggest that carotenoids, vitamin E, and vitamin C may be protective against lung cancer among nonsmokers. Food sources rich in these micronutrients may also have other constituents with independent protective effects against lung cancer.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; Carotenoids; Cohort Studies; Dairy Products; Diet; Eating; Finland; Follow-Up Studies; Fruit; Humans; Lung Neoplasms; Male; Meat Products; Middle Aged; Proportional Hazards Models; Retinoids; Risk; Selenium; Smoking; Vegetables; Vitamin E

Sodium ascorbate supplementation in drinking water inhibited subcutaneous tumor growth, enhanced levodopa methylester (LDME) chemotherapy, and increased survival of B16 melanoma-bearing mice. Antitumor activity was greatest in mice fed diets low in tyrosine and phenylalanine (restricted diet). Ascorbate partially protected against LDME-induced decrease in food intake. Primary tumor masses were smaller, more well defined, and less invasive in ascorbate-supplemented mice, and secondary tumor masses appeared encapsulated. Dehydroascorbate increased tumor growth and decreased survival. Ascorbate supplementation did not alter establishment of experimental B16-BL6 melanoma metastases but inhibited tumor outgrowth when combined with LDME chemotherapy and the restricted diet. Spontaneous metastasis was inhibited by ascorbate in mice fed the restricted diet. Ascorbate supplementation doubled plasma concentration in melanoma-bearing mice independent of diet and increased tumor concentration 3.7-fold (basal diet) and 5.6-fold (restricted diet) relative to unsupplemented mice. Tumor peroxidation also increased during ascorbate supplementation and LDME treatment.

Topics: Animals; Ascorbic Acid; Dehydroascorbic Acid; Female; Levodopa; Lung Neoplasms; Male; Malondialdehyde; Melanoma, Experimental; Mice; Neoplasm Transplantation

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

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

Potential second-stage modifying effects of 8 antioxidants on lung tumorigenesis initiated by N-bis(2-hydroxypropyl)nitrosamine (DHPN) were examined in male F344 rats. After an initial 2-week treatment with DHPN (0.1% in drinking water), rats were administered one of the antioxidants supplemented in the diet for 30 weeks. Although the incidences of lung adenomas were not affected, those of carcinomas were lowered by 2% butylated hydroxyanisole (BHA, 2 rats/20 rats), 1% butylated hydroxytoluene (BHT, 1/20), 0.8% ethoxyquin (EQ, 3/20) and 1% a-tocopherol (a-TP, 2/20) treatments as compared to the control level (9/20), while 5% sodium L-ascorbate (SA), 0.8% catechol (CC), 0.8% resorcinol (RN), and 0.8% hydroquinone (HQ) did not exert any significant effect on incidence. Quantitative analysis of adenomas and carcinomas (numbers and areas of lesions per unit area of lung section) revealed obvious inhibitory effects of SA, CC, and RN as well as BHA, BHT, EQ, and a-TP. Among the antioxidants, BHT exerted the strongest inhibitory activity. In contrast, DHPN-induced thyroid tumorigenesis was significantly enhanced by BHT (14/20) and EQ (20/20) treatments (control = 5/20). Thus the antioxidants showed opposite effects on lung and thyroid carcinogenesis in the rat.

Topics: Adenoma; Animals; Antioxidants; Ascorbic Acid; Body Weight; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Carcinoma; Catechols; Ethoxyquin; Hydroquinones; Kidney Neoplasms; Lung Neoplasms; Male; Nitrosamines; Organ Size; Rats; Rats, Inbred F344; Resorcinols; Thyroid Neoplasms; Urinary Bladder Neoplasms; Vitamin E

In a case-control study, serum levels of vitamins E, C, and A, carotenoids, total cholesterol, and retinol-binding protein along with smoking levels were studied on 59 persons newly diagnosed with lung cancer and also on matched hospitalized controls. The relative risk for smoking increased with the number of pack years of cigarettes smoked. Cases had significantly lower serum levels of carotenoids, vitamin E, and total cholesterol. Adjustment for serum cholesterol levels diminished the case-control difference for serum carotenoid levels and reduced the case-control difference for serum vitamin E levels. The results indicate that serum vitamin E may also be associated with lung cancer, possibly to a greater degree than serum retinol (vitamin A) is associated with lung cancer.

Topics: Aged; Ascorbic Acid; Carotenoids; Case-Control Studies; Cholesterol; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nutritional Status; Regression Analysis; Retinol-Binding Proteins; Smoking; Vitamin A; Vitamin E

Trauma and anaesthetics are responsible for local and general change in the organism. The characteristic changes in metabolism are caused by hormones. In addition, the increased glycogenolysis, gluconeogenesis, proteolysis and lipolysis are characteristic of this catabolic metabolism. Three groups (injured patients, patients with pulmonary disease, multiple trauma patients) showed an elevated lipid peroxidation as indicated by increased formation of TBA-reactive substances in the post-trauma or after surgery phase. The production of free radicals is supported by several stress factors. In this connection, the state of metabolism of the patients, several anaesthetics and the artificial respiration is very important. Enzymatic protecting systems (SOD, GSH-Px, Catalase) react to oxidative stress by positive adaptation. The non-enzymatic antioxidative systems (tocopherol, ascorbic acid, selen) are diminished, indicating an increased requirement.

Topics: Ascorbic Acid; Catalase; Glutathione Peroxidase; Humans; Lipid Peroxidation; Lung Neoplasms; Male; Malondialdehyde; Multiple Trauma; Postoperative Complications; Superoxide Dismutase; Vitamin E; Wounds and Injuries

The antitumour, antimetastatic and antileukemic effect of cyclophosphane and adriamycin in combination with vitamins A. E. C was studied according to the scheme developed by the authors. The preliminary administration of vitamins was established to intensify the effect of cytostatics and to lower considerably their toxic action. Cyclophosphane proved to be more effective relative to the Lewis lung carcinoma than adriamycin.

Topics: Animals; Ascorbic Acid; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Leukemia L1210; Leukemia P388; Leukemia, Erythroblastic, Acute; Leukemia, Experimental; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasms, Experimental; Sarcoma, Experimental; Vitamin A; Vitamin E

Rats were treated for 1 week each with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), 0.2% N-bis(2-hydroxypropyl)-nitrosamine (DHPN) and 0.2% N-ethyl-N-hydroxyethylnitrosamine (EHEN) in the drinking water, and then administered diet containing 5% sodium L-ascorbate (Na-AsA), 1% butylated hydroxytoluene (BHT) or 0.05% phenobarbital (PB), or weekly intraperitoneal injections of 2 mg of pepleomycin per kg body weight until week 36. Histopathological examination revealed that all exerted significant modulation effects on tumor development in the various target organs. Na-AsA was found to inhibit liver but promote renal pelvis and bladder carcinogenesis. BHT similarly decreased liver and enhanced bladder lesion development. PB, in contrast promoted hepatocarcinogenesis. However both PB and BHT were associated with increased incidences of adenomas and adenocarcinomas of the thyroid. Thus the wide-spectrum initiation model allowed confirmation of site-specific modification potential and in addition demonstrated potentiation of kidney and bladder carcinogenesis promotion by pepleomycin.

Topics: Animals; Ascorbic Acid; Bleomycin; Body Weight; Butylated Hydroxytoluene; Cocarcinogenesis; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Neoplasms, Experimental; Peplomycin; Phenobarbital; Rats; Rats, Inbred F344; Thyroid Neoplasms; Urinary Bladder Neoplasms

We conducted a population-based study of diet and lung cancer among the multiethnic population of Hawaii in 1983-1985. We completed interviews for 230 men and 102 women with lung cancer and 597 men and 268 women controls, frequency-matched to the patients by age and sex. A quantitative dietary history assessed the usual intake of foods rich in vitamins A and C and carotenoids. A clear dose-dependent negative association was demonstrated between dietary beta-carotene and lung cancer risk in both sexes. After adjusting for smoking and other covariates, the men in the lowest quartile of beta-carotene intake had an odds ratio of 1.9 (95% confidence interval, 1.1-3.2) compared to those in the highest quartile of intake. The corresponding odds ratio for women was 2.7 (95% confidence interval, 1.2-6.1). No clear association was found for retinol, vitamin C, folic acid, iron, dietary fiber, or fruits. All vegetables, dark green vegetables, cruciferous vegetables, and tomatoes showed stronger inverse associations with risk than beta-carotene. This observation suggests that other constituents of vegetables, such as lutein, lycopene, and indoles, and others, may also protect against lung cancer in humans.

Topics: Ascorbic Acid; beta Carotene; Carotenoids; Dietary Fiber; Epidemiologic Methods; Female; Folic Acid; Hawaii; Humans; Lung Neoplasms; Male; Risk; Smoking; Vegetables; Vitamin A

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

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

To find out whether keeping birds in the home is an independent risk factor for lung cancer a case-control study was carried out in four main hospitals in The Hague, The Netherlands. Forty nine patients under 65 years of age with lung cancer each were matched for age and sex with two control subjects who attended the same general practice. Data were collected on social class, cigarette smoking, intake of beta carotene and vitamin C, and alcohol consumption. It was found that smoking, birdkeeping, and a low intake of vitamin C were significantly and independently related to the incidence of lung cancer. The odds ratio for lung cancer among people who keep birds as pets was estimated to be 6.7 after adjusting for smoking and vitamin C intake. The results of this study suggest that keeping pet birds is an independent risk factor for lung cancer.

Topics: Adult; Alcohol Drinking; Animals; Animals, Domestic; Ascorbic Acid; Birds; Female; Humans; Lung Neoplasms; Male; Middle Aged; Risk Factors; Smoking

The authors describe the results of a hospital-based incident case-control study of lung cancer conducted in a high-risk region of southern Louisiana from January 1979 through April 1982. Dietary intake of carotene, retinol, and vitamin C was estimated from food frequency questionnaires administered to 1253 cases and 1274 controls. An inverse association was found between level of carotene intake and lung cancer risk, and this protective effect was specific for squamous and small cell carcinoma (odds ratio [OR] = 0.84, 95% confidence interval: 0.64-1.09, high intake). A stronger protective effect for these tumors was associated with dietary vitamin C intake (OR = 0.65, 0.50-0.87, high intake). A significant inverse gradient in risk with retinol intake was limited to adenocarcinoma (OR = 0.64, 0.44-0.94, high intake) and more pronounced among blacks.

Topics: Adult; Aged; Ascorbic Acid; Carotenoids; Diet; Female; Humans; Louisiana; Lung Neoplasms; Male; Middle Aged; Reference Values; Risk Factors; Smoking; Socioeconomic Factors; Surveys and Questionnaires; Vitamin A

Our previous study shows that 6-O-acyl derivatives of L-ascorbic acid inhibits more markedly cell growth of mouse Ehrlich carcinoma than ascorbic acid. The present study shows that 6-O-palmitoyl ascorbic acid but not ascorbic acid prolongs the lifespan of mice into which tumors such as Meth A fibrosarcoma, MM46 mammary carcinoma, Ehrlich carcinoma and sarcoma 180 are implanted. The potentiated cytotoxicity of 6-O-palmitoyl ascorbic acid is not due to an increase in duration time of the cytotoxic action, because 6-O-palmitoyl ascorbic acid is gradually inactivated during contact with tumor cells and exhibits a similar action time curve to that of ascorbic acid as shown by clonal growth assay. Cytotoxicity of 6-O-palmitoyl ascorbic acid is markedly diminished by combined addition of catalase and superoxide dismutase (SOD), as shown by dye exclusion assay, whereas the cytotoxicity was slightly reduced by either enzyme alone but not by the specifically inactivated or heat-denatured enzymes. In contrast, cytotoxicity of ascorbic acid is abolished by catalyse but not SOD. Autooxidation of 6-O-palmitoyl ascorbic acid was not inhibited by catalase plus SOD. The results indicate that cytotoxicity of 6-O-palmitoyl ascorbic acid is attributed at least partly to both hydrogen peroxide (H2O2) and superoxide (O2-.) generated at the early stage. Cytotoxicity of 6-O-palmitoyl ascorbic acid is also appreciably attenuated by singlet oxygen (1O2) scavengers such as hydroquinone, 1,4-diazobicyclo-2,2,2-octane or sodium azide, but not by hydroxyl radical scavengers including butylated hydroxytoluene, D-mannitol, benzoic acid and ethanol. Thus, in contrast to cytotoxicity of ascorbic acid mediated entirely by H2O2 initially generated, acylated ascorbic acid produces a diversity of active oxygen species including H2O2, O2-. and other species secondarily generated via disproportion, which may be additively involved in the enhanced cytotoxic action.

Topics: Animals; Antineoplastic Agents; Ascorbic Acid; Catalase; Cell Division; Cell Line; Cell Survival; Free Radicals; Humans; Leukemia, Experimental; Lung Neoplasms; Mice; Neoplasms, Experimental; Oxidation-Reduction; Superoxide Dismutase

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

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

Antitumor activity against the Lewis lung carcinoma in mice is reported for the series of 36 acridine-substituted derivatives of the antileukemia agent amsacrine. This series is the one from which the analogue N,5-dimethyl-9-[(2-methoxysulfonylamino)phenylamino]-4-acridinecarboxamide (CI-921), presently in clinical trial, was chosen. The analogues also were tested in vitro by comparing growth inhibition data [IC50 values (concentration required to reduce growth of cultured cells to 50% of that of untreated cultures)], using L1210 murine leukemia cells and HCT-8 human colon carcinoma cells. Determined IC50 values were highly dependent on the culture medium used, and it was found that the presence of ascorbate in the medium had a major effect on the stability of compounds to oxidation. A survey of 115 analogues of amsacrine indicates that a low ratio of IC50 values (HCT-8/L1210) is necessary but not sufficient for good antitumor activity against the solid tumor. DNA binding constants did not in themselves predict activity, although they were related to dose potency. Other factors, such as drug lipophilicity, acridine base strength, and drug solubility, also are involved, probably in providing effective drug distribution. It is concluded that in vitro assay data provide information useful for drug design but that other factors also are important for in vivo activity.

Topics: Amsacrine; Animals; Antineoplastic Agents; Ascorbic Acid; Drug Evaluation, Preclinical; Lung Neoplasms; Mice; Mice, Inbred DBA; Mice, Inbred Strains

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

A single intraperitoneal injection of urethane (ethyl carbamate) induces lung tumours in 80 per cent of male and 100 per cent of female NMRI mice, respectively. In the course of time the initially benign adenomatous tumours can develop into malignant adenomatosis of the lung (alveolar cell carcinoma). For an analysis of the mechanisms of tumour development and the possible interactions involved, low doses of X-rays (5-100 cGy) were administered 6 hours after urethane treatment. A significant anticarcinogenic and, also, anti-teratogenic action was observed. This implies that in both cases similar mechanisms are involved. Single injections of vitamin C or chloroquine counteract the urethane effects in the same manner as do the low doses of X-rays, but probably by different mechanisms.

Topics: Abnormalities, Drug-Induced; Animals; Ascorbic Acid; Chloroquine; Female; Lung Neoplasms; Male; Mice; Pregnancy; Urethane

Topics: Adult; Ascorbic Acid; beta Carotene; Carotenoids; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Selenium; Uric Acid; Vitamin A; Vitamins

Ascorbic acid reduces airway reactivity to inhaled bronchoconstrictor agents in man and guinea pigs. The precise mechanism(s) responsible for this effect are unknown, but in both species an acute indomethacin treatment reverses the action of the ascorbic acid. To determine if ascorbic acid promotes prostanoid synthesis and/or inhibits degradation, human lung parenchymal slices (100-200 mg) were incubated for 60 minutes in oxygenated Tyrode's solution alone or with sodium ascorbate (0.001 M-1 M) and/or methacholine (1 microM-100 microM) and/or indomethacin (0.17 microM-17 microM). Aliquots of the incubation medium were assayed by radioimmunoassay for PGE2, PGF2 alpha, thromboxane B2 and 6-keto-PGF1 alpha. Ascorbic acid increased the accumulation of all four prostanoids in the incubation medium, especially thromboxane B2 and 6-keto-PGF1 alpha. This stimulatory effect of ascorbic acid was concentration-dependent and was inhibited by indomethacin. We conclude that ascorbic acid can alter prostanoid generation by human lung tissue and this effect may, in part, explain its antibronchoconstrictor activity in man.

Topics: Ascorbic Acid; Female; Humans; Kinetics; Lung; Lung Neoplasms; Male; Methacholine Chloride; Methacholine Compounds; Prostaglandins; Smoking

The single and combined effects of (a) dietary restriction of phenylalanine and tyrosine, (b) levodopa methylester chemotherapy, and (c) megadose sodium ascorbate supplementation on experimental metastasis was determined in B16-BL6 melanoma. Dietary restriction and levodopa methylester therapy inhibited tumor outgrowth, whereas ascorbate alone was inactive. In combination, however, the effect of dietary restriction and levodopa methylester chemotherapy was augmented by sodium ascorbate. Tumor cells surviving this combination therapy (treated population) were isolated from the lungs of treated mice, and proved to be tumorigenic when inoculated SC into the back of naive mice. The resulting tumors grew more slowly than those produced by inoculation of similarly isolated control cells (control population), irrespective of whether the diet was adequate or deficient in phenylalanine and tyrosine. Failure of the treated tumor cell population to exhibit reduced sensitivity to the combination chemotherapy or, unlike the control population, to exhibit variation in pigmentation levels, suggests that the restriction of phenylalanine and tyrosine during drug therapy alters the tumor response to reduce heterogeneity and perhaps interferes with the emergence of drug resistance.

Topics: Animals; Ascorbic Acid; Diet; Female; Levodopa; Lung Neoplasms; Melanoma; Mice; Mice, Inbred Strains; Phenylalanine; Tyrosine

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

This report presents preliminary findings from 3 case-control studies in Hawaii in which we are examining the relationship of dietary vitamin A and ascorbic acid intake to the risk for cancers of the lung, bladder, and prostate. All 3 studies involved home interviews of cancer patients and neighborhood controls and use of quantitative dietary history method. In the lung cancer study, we found an inverse dose-response effect for total vitamin A intake in males only, with an odds ratio of 1.8 (P less than .05) for the lowest intake quartile relative to the highest; we found no association for ascorbic acid. In the bladder cancer study, we found lower (but not statistically significant) mean intakes of both vitamins in patients compared with controls, with the effect stronger for ascorbic acid. In the prostate cancer study, no effect was detected for total vitamin A or ascorbic acid in men less than 70 years old, but a direct association of vitamin A only with a dose-response gradient was found for men 70 years or older (odds ratio = 1.87; P less than .05, for the highest relative to the lowest intake quartile). Our findings at present indicate that vitamin A has a protective effect against lung and bladder cancers but not against prostate cancer and that ascorbic acid has a protective effect against bladder cancer as well. In our later analyses, we will examine the possibility that the effects of vitamin A vary with histologic type and that this may account for the lack of an association with lung cancer in women.

Topics: Ascorbic Acid; Diet; Ethnicity; Female; Hawaii; Humans; Japan; Lung Neoplasms; Male; Prostatic Neoplasms; Registries; Risk; Urinary Bladder Neoplasms; Vitamin A; White People

Topics: Ascorbic Acid; Diet; Female; Hawaii; Humans; Lung Neoplasms; Male; Vitamin A

A case-control study was conducted based on 427 white males with lung cancer of the squamous, small cell, and adenocarcinoma histologic subtypes and 1,094 white male controls admitted to Roswell Park Memorial Institute between the years 1957 and 1965. The relation between selected dietary factors and lung cancer risk was examined for each histologic subtype while controlling for past cigarette use. Dietary vitamin A was found to be negatively associated with risk for squamous cell and small cell carcinoma, but not for adenocarcinoma of the lung. No significant association was observed, however, between dietary vitamin C, fats, or fiber and any of the lung cancer subtypes. These results suggest that the apparent protective effect of vitamin A in lung cancer may be histologic type-specific.

Topics: Adenocarcinoma; Adult; Aged; Alcohol Drinking; Ascorbic Acid; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Diet; Dietary Fats; Dietary Fiber; Humans; Lung Neoplasms; Male; Middle Aged; Risk; Smoking; Vitamin A

The authors conducted a case-control study among the multiethnic population of Hawaii to test the hypotheses that lung cancer risk is inversely associated with dietary intake of total vitamin A, carotene, and vitamin C. Detailed dietary interviews were completed between September 1979 and October 1982 for 364 primary lung cancer patients and 627 general population controls matched on age and sex. After adjusting for a number of potentially confounding variables, including ethnicity, smoking history, and occupation, evidence was found that total vitamin A intake (food sources plus supplements), vitamin A intake from food sources only, and carotene intake were each inversely associated with lung cancer risk in males, but not in females. Among males, a monotonic dose-response relationship was found only for total vitamin A intake. However, a comparison of the lowest and highest quartiles of intake gave similar results for each of the three measures of nutrient intake: total vitamin A (odds ratio (OR) = 1.8; 95% confidence limits (CL) = 1.1-3.1), vitamin A from foods (OR = 2.0; 95% CL = 1.2-3.5), and carotene (OR = 2.2; 95% CL = 1.3-3.7). Similar analyses revealed no significant association between dietary vitamin C intake and lung cancer risk.

Topics: Aged; Ascorbic Acid; Carotenoids; Diet; Epidemiologic Methods; Ethnicity; Female; Hawaii; Humans; Lung Neoplasms; Male; Middle Aged; Risk; Sex Factors; Smoking; Vitamin A

Topics: Animals; Ascorbic Acid; Breast Neoplasms; Fluorouracil; Humans; Lung Neoplasms; Mice; Neoplasms; Neoplasms, Experimental; Orthomolecular Therapy; Thiamine; Thiamine Pyrophosphate; Transketolase; Vitamin A

A squamous cell carcinoma (ASB XIII) and a large cell carcinoma (ASB XIV) induced from mouse lung cells by chrysotile asbestos were established in serial transplant in BALB/c mice. New hosts were treated with retinoids by ip injection at 10 mg/kg 5 days/week. Growth inhibition of ASB XIII was 58%-64% (P less than 0.005) after treatments with all-trans retinoic acid, 52% after trimethylmethoxyphenyl analog, ethyl ester, 26% (not significant) after 13-cis retinoic acid. Growth inhibition of ASB XIV was 39% (P less than 0.02) after injections of all-trans retinoic acid, and 33% (P greater than 0.05) after trimethylmethoxyphenyl analog, ethyl ester. After daily oral administration of 10 mg/kg of all-trans retinoic acid in feed, there was 61%-81% inhibition (P less than 0.005) of ASB XIII. Growth of ASB XIII was not significantly inhibited by daily im injections of 200 mg/kg of vitamin C.

Topics: Animals; Ascorbic Acid; Body Weight; Carcinoma; Carcinoma, Squamous Cell; Diet; Female; Injections, Intraperitoneal; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Probability; Retinoids

Incidence rates for many sites of cancer show wide variations among the main ethnic groups in Hawaii (Caucasians, Japanese, Chinese, Filipinos, and Hawaiians). Major shifts in cancer rates among migrants to the islands suggest that environmental factors are at least in part responsible for these variations. One prominent area of difference among these ethnic populations is their diets, which can vary substantially, not only in the consumption of particular food items but also in mean nutrient intakes. In aggregate correlational analyses based on data from representative samples of these ethnic groups and corresponding population-based cancer incidence rates, we found significant associations between ethnic-sex-specific intakes of dietary fat (including total fat, as well as animal, saturated, and unsaturated fats) and breast, endometrial, and prostate cancers. Animal protein intake showed associations similar to those for dietary fat, but these two nutrients were highly correlated in the data. Cholesterol intake showed significant correlations with lung and laryngeal cancers. Analyses of both nutrient and food item data suggested an association of stomach cancer incidence with the consumption of fish products, particularly dried/salted fish, and with a lower intake of vitamin C. Preliminary findings from ongoing case-control studies showed the following relationships: an inverse association between lung cancer risk and the intake of food sources of vitamin A, especially foods containing carotenes; an inverse association between cancers of the lower urinary tract and vitamin A consumption, especially from supplements; a positive association between prostate cancer risk and dietary fat intake in men above age 69, but not in younger men; and a positive association between breast cancer risk and the intake of dietary fat (particularly saturated fat) and animal protein in postmenopausal women, especially the Japanese. Two large cohorts (50,000 and 5,000 subjects) on whom dietary information was collected between 1975 and 1980 are being followed prospectively for their occurrence of cancer.

Topics: Age Factors; Aged; Ascorbic Acid; Breast Neoplasms; Diet; Dietary Fats; Ethnicity; Female; Hawaii; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Prostatic Neoplasms; Risk; Urologic Neoplasms; Vitamin A

Topics: Alpha Particles; Animals; Ascorbic Acid; Female; Lung Neoplasms; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Plutonium; Rats; Rats, Inbred F344; Time Factors

A systematic study of vitamin C blood levels in patients with cancer and an evaluation of their modifications when the patients were orally treated with daily large doses of ascorbic acid (5g/day) have been carried out. For excluding any interference on intestinal vitamin C absorption, all patients with digestive tract cancer have been excluded. Our first results concern 24 lung cancer and 35 bladder cancer patients, operable or not, of different sex and age. The study has shown hypovitaminosis C subclinic conditions for the greater part of subjects: in fact the average haematic rate of ascorbic acid approaches to lower level of physiologic range, appearing very low particularly for the younger patients. Periodic haematic dosages of vitamin C of unoperable and operated patients treated with large doses of ascorbic acid, have shown a rapid increase of its blood concentration which frequently has been very over 1500 micrograms%, the higher level of normal range. These high vitamin haematic levels, generally constant during the time, appear usefull in increasing the defence reactions of the cancerous patient.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinoma; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Urinary Bladder Neoplasms

Plasma and buffy-coat vitamin C were estimated in 158 samples from 139 lung-cancer patients, at all stages of the disease. Most samples showed hypovitaminosis C in both estimations: 64% had plasma, and 25% buffy-coat values below the thresholds for incipient clinical scurvy (0.3 mg% and 10 micrograms/10(8) cells respectively). Levels were diet-dependent and could be increased by oral supplements. Levels were low both in tumour-bearing patients and in those clinically free of disease after resection. The latter had particularly low values during the first 6 months, indicating the utilization of vitamin C in surgical repair. The vitamin C content of 13 primary lung tumours was assayed: tumours had a higher vitamin C content (mean 111.6 +/- 55.1 micrograms/g tissue) than normal lung (58.5 +/- 20.4 micrograms/g). Mononuclear cells from normal individuals show a higher vitamin C content than polymorphs, but in lung-cancer patients the expected correlation of buffy-coat vitamin C with the proportion of lymphocytes in peripheral blood was obscured by an inverse correlation in patients with relative lymphocytosis (greater than or equal to 25% lymphocytes), confirmed by an inverse correlation of the proportion of lymphocytes in peripheral blood with mononuclear-cell vitamin C in 14 patients in whom this was measured. These correlations were unaffected by controlling for plasma values, and indicate the utilization of vitamin C in lymphocyte-related anti-tumour mechanisms. Vitamin C is necessary for phagocytosis and for the expression of cell-mediated immunity. In view of the increasing circumstantial evidence that immune mechanisms exert some measure of control on tumour extension and metastasis in man, the effect of supplementation with vitamin C in lung-cancer patients on survival should be tested in a clinical trial.

Topics: Adult; Aged; Ascorbic Acid; Ascorbic Acid Deficiency; Carcinoma, Bronchogenic; Diet; Female; Humans; Immunity, Innate; Leukocyte Count; Leukocytes; Lung Neoplasms; Lymphocytes; Male; Middle Aged; Seasons

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

Topics: Ascorbic Acid; Diet; Dose-Response Relationship, Drug; Fruit; Gastrointestinal Neoplasms; Humans; Lung Neoplasms; Male; Mouth Neoplasms; Risk; Vegetables; Vitamin A

Topics: Ascorbic Acid; Diagnosis, Differential; Humans; Lung Diseases, Obstructive; Lung Neoplasms; Neutrophils

Topics: Animals; Ascorbic Acid; Diterpenes; Dust; Glass; Lung; Lung Neoplasms; Male; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Retinyl Esters; Vitamin A

Topics: Animals; Ascorbic Acid; Lung Neoplasms; Male; Melanoma; Mice; Mice, Inbred C57BL; Neoplasms, Experimental

Three cases are described, 2 of Hodgkin's disease and a further case of bronchial carcinoma, where high dosage ascorbic acid treatment appeared to be associated with the development of potentially dangerous symptoms. It is suggested that mega ascorbic acid therapy should be given with caution in malignant disease, with a slow build-up over several days to high levels of dosage.

Topics: Adult; Aged; Animals; Antineoplastic Agents; Ascorbic Acid; Bronchial Neoplasms; Carcinoma, Small Cell; Dyspnea; Fever; Hodgkin Disease; Humans; Lung Neoplasms; Male; Neoplasms; Orthomolecular Therapy

Topics: Adult; Ascorbic Acid; Breast Neoplasms; Child; Female; Humans; Leukocytes; Lung Neoplasms; Mouth Neoplasms; Neoplasms; Rectal Neoplasms; Skin Neoplasms; Urinary Bladder Neoplasms; Uterine Cervical Neoplasms

Topics: Aminopyrine; Animals; Ascorbic Acid; Carcinogens; Female; Lung Neoplasms; Male; Neoplasms, Experimental; Nitrites; Nitrosamines; Rats

Lung adenomas were induced in strain A mice by chronic treatment with N-nitroso compounds (given in drinking water) and with amines or ureas in food plus NaNO2 in drinking water. We studied the effects of varying the concentrations of three N-nitroso compounds and NaNO2 concentration in the morpholine plus NaNO2 and methylurea plus NaNO2 systems. Sodium ascorbate (NaASC) at the highest level tested (11.5 or 23 g/kg food) gave 89-98% inhibition of adenoma induction by the NaNO2 plus piperazine, morpholine, and methylurea systems. In 7 groups, NaASC produced increases of 15-59% in adenoma induction by nitrosomorpholine (NM) and mononitrosopiperazine (MNP), possibly because the mice consumed more of the nitrosamine solution. Adenoma induction by morpholine plus NaNO2 was strongly inhibited by gallic acid, moderately inhibited by caffeine, and unaffected by thiocyanate (all added to the food). Gallic acid inhibited or had no effect on the action of NM and MNP. We discussed the proposal that NaASC (or perhaps gallic acid) be administered with readily nitrosatable drugs.

Topics: Adenoma; Amines; Animals; Ascorbic Acid; Caffeine; Dose-Response Relationship, Drug; Gallic Acid; Lung Neoplasms; Male; Methylurea Compounds; Mice; Mice, Inbred A; Morpholines; Neoplasms, Experimental; Nitrites; Nitroso Compounds; Piperazines; Thiocyanates; Urea

Topics: Adolescent; Aged; Ascorbic Acid; Carcinoma; Child; Child, Preschool; Humans; Leukemia, Lymphoid; Leukocytes; Lung Neoplasms; Male; Middle Aged; Neoplasms; Skin; Skin Neoplasms

Normal and tumour tissues from rats, blood from normal and tumour bearing rats, and normal human blood were examined using the electron paramagnetic resonance (epr) technique. At low temperature a triplet epr signal, which is known to be produced by a NO-haemoprotein complex, was detected in some tumour samples and in decaying normal liver. At room temperature all of the tumour samples examined gave a doublet signal. This signal was also detected in blood but not in other normal tissues. The signal has a g value of 2·0054 ± 0·0002 and a hyperfine splitting of 1·80 ± 0·05 G and is assigned to the ascorbyl free radical. Model experiments suggest that the appearance of detectable concentrations of this radical result from a disturbance of the normal state of the ascorbic acid, dehydroascorbic acid redox system. It was verified that cell division is not responsible for the ascorbyl radical although autolysis may be involved. A possible relationship between the formation of ascorbyl radicals and other paramagnetic species in tumours is discussed.

Topics: Animals; Ascorbic Acid; Autolysis; Blood Proteins; Carcinoma 256, Walker; Carcinoma, Hepatocellular; Cell Division; Electron Spin Resonance Spectroscopy; Liver Neoplasms; Lung Neoplasms; Methods; Models, Biological; Models, Chemical; Neoplasms; Nitric Oxide; Oxidation-Reduction; Rats; Sarcoma, Yoshida; Temperature

Topics: Ascorbic Acid; Female; Humans; Lung Neoplasms; Male; Radiation Injuries; Radiotherapy

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

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

Topics: Androgens; Antibiotics, Antineoplastic; Antineoplastic Agents; Ascorbic Acid; Azirines; Bronchial Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Cyclophosphamide; Drug Synergism; Fluorouracil; Glucocorticoids; Humans; Hydrazines; Injections, Intramuscular; Injections, Intravenous; Lectins; Lung Neoplasms; Mechlorethamine; Mercaptopurine; Mesothelioma; Methotrexate; Phenylbutazone; Pleural Neoplasms; Thiotepa; Vinblastine

Topics: Ascorbic Acid; Bronchial Fistula; Bronchiectasis; Empyema; Empyema, Pleural; Humans; Lung Abscess; Lung Neoplasms; Oxytetracycline; Penicillins; Pneumonectomy; Postoperative Complications; Pulmonary Fibrosis; Punctures; Streptomycin; Thiamine