DESCRIPTION: (Applicant's Description) Cigarette smoking, which is
considered as a model environmental exposure, has been the major cause of
lung cancer in United States. Dietary consumption of fruits and vegetables
which are rich in antioxidants, such as vitamin C, has shown protective
effects against smoking-related cancer risk in several epidemiological
studies. We hypothesize that daily oral vitamin C supplementation decreases
carcinogen- or free radical-induced DNA damage in lymphocytes (surrogate
tissue) of current smokers. To test this hypothesis, we propose to analyze
two biomarkers, i.e., smoking-related PAH-DNA adducts and oxidative DNA
damage (8-OHdG) by 32-P-postlabeling assay in lymphocyte DNA of current
smokers. This project will use blood samples from a previously completed
vitamin C intervention trial involving 200 current smokers. In the original
project, subjects received oral supplementation of vitamin C in doses of 1
or 4 grams per day or placebo for 4 months. Serum ascorbic acid level was
measured by HPLC prior to randomization and one month after treatment on
vitamin C. Effects of vitamin C supplementation on the individual
susceptibility to genotoxic agents was evaluated by quantification of
bleomycin-induced chromosomes breaks in short-term peripheral lymphocyte
cultures. The current proposal intends to evaluate the efficacy of oral
vitamin C supplementation on DNA damage in the same study subjects. Fifty
samples each from the high dose group (4 g per day) and the placebo group
will be evaluated at 2 time points. Correlations between serum vitamin C
level, mutagen sensitivity and DNA-damaged induced by smoking will be
evaluated. Results of this study are expected to demonstrate the
feasibility of DNA adducts as reliable biomarkers in the risk assessment for
smoking-related cancer and to show that vitamin C offers protection by
scavenging free radicals, thus decreasing the oxidative DNA damage.
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