Effects of antioxidant supplementation with vitamins C and E: Reduction of benzo[a]pyrene (BP)-DNA adducts in female smokers Frederica P. Perera, LaVerne A. Mooney, Elizabeth Garduno, Ann M. Madsen, Manuela A. Orjeula, Wei-Yann Tsai, Deliang Tang. Columbia University, Mailman School of Public Health, New York, NY. Introduction: The purpose of this randomized double-blind placebo-controlled clinical trial was to assess the effects of daily supplementation with 500 mg vitamin C and 400 IU vitamin E (á- TOC) on biomarkers of procarcinogenic DNA damage in the leukocytes of smokers, and to determine the time course and reversibility of effects. We earlier showed that benzo [a] pyrene (BP)- DNA adducts in leukocytes are a marker of lung cancer risk in smokers (Tang et al., Cancer Res. 2001;61:6708-12), and thus a useful intermediate endpoint in chemoprevention trials. Methods: Blood samples and questionnaire data were collected from smokers at baseline, randomization, and at 3 month intervals. A final sample was collected at 21 months, after the treated group had been on placebo for 6 months. BP-DNA adducts were analyzed by HPLC/fluorescence, cotinine by GC, á-TOC by HPLC. The linear regression model included pre-treatment BP-DNA adducts and cotinine, and treatment. Subjects were stratified by gender. Results: Among women, at the 12 month timepoint, the mean adduct level in the treated group was 41% lower than in the placebo group (p=0.006, n=70). At 15 months, adducts were reduced 29% in treated, compared to untreated women (p=0.057, n=72). However, there was no effect at 6 months (p=0.693, n=61). The finding is consistent with the observation that plasma á-TOC levels did not differ between treated and untreated women at 6 months (p=0.090); but did at 12 months (p=0.002). At 21 months, 6 months after all subjects began receiving placebo, there was no difference between the 2 groups in either BP-DNA adducts (p=0.465) or á-TOC (p=0.417). Among men, there was no effect of treatment on BP-DNA adducts at any timepoint, despite significantly elevated plasma á-TOC levels in the treatment group beginning at 3 months Conclusion: This study demonstrates that supplementation with relatively low levels of antioxidants results in a significant reduction in DNA damage/potential cancer risk among women smokers. The protective effect was not evident until >6 months of treatment, consistent with the estimated half-life of adducts (10-15 weeks), indicating that 6 months is not long enough for vitamins to have a benefit in terms of risk reduction. The finding that the protective effect disappeared after 6 months of placebo indicates the need for sustained supplementation to achieve health benefits. The observed gender difference does not appear to be due to lack of compliance and may reflect the influence of hormonal or behavioral factors that promote the formation of DNA adducts so that antioxidants play a more important role in risk modulation. There is prior evidence that women smokers have a higher lung cancer risk than men with the same smoking history. While the results of this trial demonstrate a protective role of antioxidant supplementation in women, the best way for smokers to reduce their cancer risk remains smoking cessation. AACR Abstract Number: R3893 AACR Abstract #LB-3, 2003 AACR Abstract #3990, 2003 AACR bstract #3991, 2003 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.