Chromosomal damage rate, aging, and diet.

Chromosomal damage as measured by frequency of translocations, acentric fragments, telomere shortening, nondisjunction, chromosome loss, aneuploidy, and micronucleus formation has been shown to increase progressively with age. Using the cytokinesis-block micronucleus technique, which provides an efficient measure of chromosomal breakage and loss, we have been able to show that aging can explain at least 25% of the variation in chromosomal damage rate in lymphocytes from both males and females. We have also performed cross-sectional and placebo-controlled intervention studies to determine the relationship between the micronucleus (MN) frequency in lymphocytes and diet, and blood status for vitamins C, E, B12, and folic acid. Our studies have shown that MN frequency in the 41- to 60-year age group is significantly lower in vegetarians when compared to nonvegetarians, but the reverse was true in males aged between 20 and 40 years. This was accounted for by a deficient/low B12 status in vegetarian males; there was no difference in the MN frequency of vegetarian and nonvegetarian subjects aged between 61 and 90 years. Results from this study also showed significant negative correlations of MN frequency with folic acid and vitamin B12 but not with vitamin C or vitamin E. In separate studies on healthy men aged 50-70, we have verified the significant negative correlation between vitamin B12 status in plasma and MN frequency (r = -0.315, p = 0.013) in subjects who were not vitamin B12 deficient and observed a significant positive correlation between MN frequency and homocysteine status (r = 0.414, p = 0.0086) in those men who were not vitamin B12 and/or folate deficient. These data suggest that MN frequency is minimized when plasma B12 is above 300 pmol/L and plasma homocysteine is below 7.5 mumol/L. Double-blind placebo-controlled intervention studies conducted over four months have shown that above RDI intake of vitamin E (30 x RDI) or folic acid (10 x RDI) did not produce a significant reduction in MN frequency in men aged 50-70 years. In the latter case plasma homocysteine was reduced from a mean value of 9.33 mumol/L to 8.51 mumol/L, a level that does not correspond with minimization of MN frequency. We have also tested the hypothesis that moderate wine drinking can protect against the DNA-damaging effect of hydrogen peroxide and found that there was a strong ex vivo inhibition (> 70%) of hydrogen peroxide-induced MN frequency by plasma samples from blood collected one hour after consumption of red or white wine, as compared to plasma samples collected immediately before wine consumption (p = 0.0008). However, only samples following red wine consumption produced a significant reduction in baseline MN frequency. The above results suggest that chromosome damage can be modulated, under selected circumstances, by diverse dietary factors.