OXIDATIVE DNA-DAMAGE MEASURED IN HUMAN-LYMPHOCYTES - LARGE DIFFERENCES BETWEEN SEXES AND BETWEEN COUNTRIES, AND CORRELATIONS WITH HEART-DISEASE MORTALITY-RATES

The 'antioxidant hypothesis' proposes that vitamin C, vitamin E, carot enoids, and other antioxidants occurring in fruit and vegetables affor d protection against heart disease and cancer by preventing oxidative damage to lipids and to DNA, respectively. To test elements of this hy pothesis, we have measured blood levels of dietary antioxidants, and 8 -oxodeoxyguanosine (8-oxo-dG) concentrations in lymphocyte DNA, in hea lthy men and women from five European countries: France, Ireland, The Netherlands, Spain, and the U.K. Volunteers, aged 25-45, all nonsmoker s, gave blood samples before and after a 12-wk carotenoid supplementat ion regime. Vitamin C was measured in plasma and vitamin E and caroten oids were measured in serum by high-performance liquid chromatography (HPLC). 8-oxo-dG was assayed by HPLC (with coulometric detection) in D NA isolated from lymphocytes from the same blood samples. Mean values were calculated for groups of volunteers at each sampling time accordi ng to country, sex, and supplementation (between 9 and 24 individual s amples contributing to each mean). We found that 8-oxo-dG levels in ly mphocyte DNA vary significantly according to sex and country. A low me an 8-oxo-dG concentration is seen in DNA of women from all five countr ies, and of men from France and Spain. 8-oxo-dG is significantly highe r (up to about threefold) in lymphocyte DNA from men in Ireland and th e U.K. Oxidative DNA damage is not significantly affected by carotenoi d supplementation; nor is there any association with mean baseline lev els of antioxidants, which are generally similar in the five countries . The five countries sampled lie on an axis from northern to southern Europe with a steep gradient:in terms of premature heart disease. Ther e is a strong association between premature coronary heart disease mor tality in men and the mean levels of 8-oxo-dG for the five countries ( r = 0.95, P < 0.01). Women have low coronary heart disease mortality r ates, which do not correlate with 8-oxo-dG. In terms of cancer deaths, only colorectal cancer in men shows a significant positive correlatio n (r = 0.91, P < 0.05), and stomach cancer in women is negatively corr elated with DNA oxidation (r = -0.92, P = 0.01).