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The effects of age on the metabolism of chemical carcinogens and inducibility of O6-methylguanine methyltransferase.

Some aspects of the age-dependence of the metabolic activation of three classes of chemical carcinogen (polycyclic hydrocarbons, N-nitrosamines and aromatic amines) are considered. In general, and as with other xenobiotic agents, metabolism is low in fetal tissue, increases with maturation and decreases in old age. In a single-dose hydrocarbon carcinogenesis model system, a decrease in tumour incidence is correlated with increasing age at treatment, although other factors such as cell turnover at the time of carcinogen treatment are also correlated with this disease. Evidence is presented, in addition, that the induction of rat hepatic O6-methylguanine-DNA methyltransferase activity by the metabolism-requiring hepato-carcinogen 2-acetylaminofluorene increases with age.