ANTIOXIDANT SUPPLEMENTATION DECREASES OXIDATIVE DNA-DAMAGE IN HUMAN-LYMPHOCYTES

The association between high intake of fruit and vegetables and low in cidence of certain cancers is well established. Dietary antioxidants p resent in these foods are thought to decrease free radical attack on D NA and hence to protect against mutations that cause cancer, but this causal mechanism remains conjectural. We have adopted a molecular epid emiological approach to this question, based on a modified alkaline si ngle-cell gel electrophoresis assay (''comet assay'') which specifical ly detects oxidation of pyrimidines in the DNA of human lymphocytes. I n a survey of men 50-59 years of age living in the northeast of Scotla nd, smokers initially showed significantly more base damage than nonsm okers. Correlations between oxidative base damage and plasma concentra tions of various antioxidants were generally negative but not statisti cally significant.Supplementation of the diet for 20 weeks with vitami n C (100 mg/day), vitamin E (280 mg/day), and beta-carotene (25 mg/day ) resulted in a highly significant (P < 0.002) decrease in endogenous oxidative base damage in the lymphocyte DNA of both smokers and nonsmo kers. In addition, lymphocytes of antioxidant-supplemented subjects sh owed an increased resistance to oxidative damage when challenged in vi tro with H2O2. These findings strongly support the hypothesis that fru it and vegetables exert a cancer-protective effect via a decrease in o xidative damage to DNA.