Dietary factors affecting spontaneous chromosomal damage in man

The data summarized above demonstrate that dietary and nutritional factors can influence spontaneous rates of chromosomal damage in laboratory animals, and suggest strongly that certain of these dietary factors may exert a quantitatively significant influence on spontaneous chromosomal damage frequencies in human populations. Among a total of 77 splenectomized human subjects examined in two separate studies, consumption of caffeinated beverages, mild folate deficiency, and consumption of calcium supplements by older women were statistically associated with higher frequencies of micronucleated cells. Subjects who reported taking dietary supplements of vitamins C, E, or A had significantly lower values. Age was strongly associated with micronucleus frequency when other factors were not considered, but was only weakly associated when all factors were included in a multiple regression analysis. Followup studies in laboratory animals established that caffeine is a strong inducer of micronuclei in marginally folate-deficient mice, but not in folate-sufficient mice. Deficiencies of magnesium or zinc, two metals required for DNA synthesis and/or maintenance of chromatin structure, increase the rate of spontaneous chromosomal damage in laboratory animals. These and other data discussed above suggest that dietary deficiencies of nutrients required for nucleotide synthesis, such as folate, vitamin B12, and magnesium, may increase spontaneous chromosomal damage, and may strongly influence the genotoxic response to other dietary factors. It is critically important to systematically investigate the quantitative importance of the above factors in man, using 1) human cross-sectional epidemiology and supporting animal data to identify potentially significant risk factors and to elucidate the mechanisms of interaction among these factors, and 2) controlled intervention studies in man to determine the quantitative significance of these factors in human populations. We feel the use of splenectomized populations, in which chromosomal damage is easily monitored and in which the marker of damage is temporally responsive to removal of risk factors, will play an important role in the intervention phase of such studies.