Oxidative DNA damage measured in human lymphocytes: large differences between sexes and between countries, and correlations with heart disease mortality rates

Abstract

The 'antioxidant hypothesis' proposes that vitamin C, vitamin E, carotenoids, and other antioxidants occurring in fruit and vegetables afford protection against heart disease and cancer by preventing oxidative damage to lipids and to DNA, respectively. To test elements of this hypothesis, we have measured blood levels of dietary antioxidants, and 8-oxodeoxyguanosine (8-oxo-dG) concentrations in lymphocyte DNA, in healthy men and women from five European countries: France, Ireland, The Netherlands, Spain, and the U.K. Volunteers, aged 25 45, all nonsmokers, gave blood samples before and after a 12-wk carotenoid supplementation regime. Vitamin C was measured in plasma and vitamin E and carotenoids were measured in serum by high-performance liquid chromatography (HPLC). 8-oxo-dG was assayed by HPLC (with coulometric detection) in DNA isolated from lymphocytes from the same blood samples. Mean values were calculated for groups of volunteers at each sampling time according to country, sex, and supplementation (between 9 and 24 individual samples contributing to each mean). We found that 8-oxo-dG levels in lymphocyte DNA vary significantly according to sex and country. A low mean 8-oxo-dG concentration is seen in DNA of women from all five countries, and of men from France and Spain. 8-oxo-dG is significantly higher (up to about threefold) in lymphocyte DNA from men in Ireland and the U.K. Oxidative DNA damage is not significantly affected by carotenoid supplementation; nor is there any association with mean baseline levels 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. There is a strong association between premature coronary heart disease mortality 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 rates, which do not correlate with 8-oxo-dG. In terms of cancer deaths, only colorectal cancer in men shows a significant positive correlation (r = 0.91, P < 0.05), and stomach cancer in women is negatively correlated with DNA oxidation (r = -0.92, P = 0.01).

Effect of vitamin levels on biomarkers of exposure and oxidative damage—The EXPAH study

“…Both M1dG and 8-oxodG adducts showed a weak correlation with vitamin A levels, which persisted for M1dG only at the mutivariate analysis, where the data were adjusted for possible confounders; in this analysis, age became the predominant independent determinant of oxidative damage. Similar findings were reported by a study conducted in five European countries (31), and by a study involving men on high fruit and vegetable diets (32). A study involving coke-oven workers who took vitamin supplements showed that the excretion of 8-oxodG adducts was decreased compared to those workers that took no vitamins (33).…”

Persistent oxidative stress in colorectal carcinoma patients

“…General characteristic of the analytical parameters of the study groups is described in the 14 We did not, however, find any difference in 8-oxodGuo level between men and women in the studied groups.…”

“…14,15 We examine whether this level in lymphocytes DNA is higher in colon cancer patients when compared to the control group. Factors that may influence oxidative stress such as antioxidant vitamins and uric acid were also determined.…”

The relationship between biomarkers of oxidative DNA damage, polycyclic aromatic hydrocarbon DNA adducts, antioxidant status and genetic susceptibility following exposure to environmental air pollution in humans

“…Antioxidants present in the diet in theory should provide protection against the deleterious effects of xenobiotics that have the potential or lead to the induction of oxidative stress [31] and [32]. There was no significant correlation found for individuals between the levels of vitamin A, vitamin E, vitamin C and folate with individuals from five European countries [33]. A study involving men on high fruit and vegetable diets again failed to find any correlation with level of 8-oxodG adducts excreted into the urine [34].…”