Ames, B. N., and Gold, L. S. Cell Division and DNA Lesions are key factors in mutagenesis, carcinogenesis, and cancer prevention. In: Encyclopedia of Cancer (J. R. Bertino, ed.), Orlando, FL: Academic Press, Volume 2, pp. 1120-1128 (1996).
Mechanistic studies of carcinogenesis indicate an important role of endogenous oxidative damage to DNA that is balanced by elaborate defense and repair processes. Also key is the rate of cell division, which is influenced by hormones, growth, cytotoxicity, and inflammation, as this determines the probability of converting DNA lesions to mutations. These mechanisms underlie many epidemiologic observations. Epidemiological evidence indicates that avoidance of smoking, increased consumption of fruits and vegetables, and control of infections will have a major effect on reducing rates of cancer. A substantial reduction in breast cancer is likely to require modification of sex hormone levels, and development of practical methods for doing so is a high research priority. Animal cancer tests are usually done on synthetic chemicals at the maximum tolerated dose (MTD) of the chemical. These results are being misinterpreted to mean that low doses of synthetic chemicals and industrial pollutants are relevant to human cancer. About half of the chemicals tested, whether synthetic or natural, are carcinogenic to rats or mice at these high doses. A plausible explanation for the high proportion of positive results is that testing at the MTD frequently can cause chronic cell killing and consequent cell replacement, which is a risk factor for cancer that can be limited to high doses.
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Last updated: November 25, 1996