The effect of antioxidant supplementation on oxidative damage in smokers

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Here, we have investigated the relationship between antioxidant supplementation and 8-hydroxy-2’-deoxyguanosine (8-OHdG) in WBC among smokers. 8-OHdG is a biomarker of oxidative damage associated with lung cancer risk. Previously, we reported results from a randomized clinical trial of antioxidant supplementation (500 mg vitamin C and 400 IU vitamin E (dl-alpha-tocopherol) daily) on benzo(a)pyrene (BP)-DNA adducts in a population of smokers (n= 284)(1). In that study, after 15 months of treatment, women in the treatment group had a significantly greater reduction in BP-DNA adducts compared to women in the placebo group, with this effect more pronounced with the null genotype for GSTM1 (a detoxification enzyme). The present analysis involves the smaller subset of the trial population (n=84) who had repeat measures of 8-OHdG in WBD at baseline and at 12 and/or 15 months of follow-up (“endpoint”). METHODS: 8-OHdG was measured by HPLC (Huang X. et al. Importance of complete DNA digestion in minimizing variability in the analysis of 8-oxo-dG as a biomarker of cancer risk. Free Radical Biol. Med. 31:1341-1351, 2001). Linear regression was used to evaluate the effect of antioxidant supplementation on changes in 8-OHdG from baseline to the endpoint. Based on our previous results, we also explored differences in effects of supplementation by gender or GSTM1 status (stratifying the sample by gender and GSTM1 separately). Our results were not meaningfully changed after adjusting for potential confounders (e.g., sex, heavy smoking, GSTM1 status, and obesity), so crude results are reported. RESULTS: Overall, antioxidant supplementation did not significantly predict a change in oxidative damage from baseline to the endpoint (n=84, β=-9.3798, p=0.11). However, supplementation was significantly associated with a smaller increase in 8-OHdG over the treatment period in women (n=38, β=-14.53, p=0.04), but not men (n= 46, p>0.05). Supplementation significantly predicted a greater decrease in 8-OHdG during the treatment period among GSTM1 ++/+- individuals (n=58, β=-17.32, p=0.03) but not among GSTM1 -/- individuals (n=26, β=5.5, p=0.35). CONCLUSIONS: In this subset of participants in a clinical trial of antioxidant vitamin supplementation among smokers, we found that female smokers assigned to antioxidant supplementation demonstrated reduced 8-OHdG by 15 months treatment compared to those assigned to the placebo, consistent with the trial results reported for BP-DNA adducts, another biomarker of lung cancer risk. This finding contributes to a body of literature suggesting gender differences in the effects of antioxidant supplementation on cancer risk and that future research on antioxidant supplementation on cancer risk should consider men and women separately. Regardless of the effects of antioxidants on cancer risk, smoking cessation remains the most important intervention for public health. (1) Mooney LA, et al. Antioxidant vitamin supplementation reduces benzo(a)pyrene-DNA adducts and potential cancer risk in female smokers. Cancer Epidemiol Biomarkers Prev. 2005 Jan;14(1):237-421.