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.