Metabolism of diethylnitrosamine by human liver slices in vitro.

Abstract

THE occurrence of carcinogenic nitrosamines in various environmental conditions and the possible hazard to human subjects and animals exposed to them have been discussed in several reviews1–4. A wide range of species is susceptible to the carcinogenic action of the nitrosamines but there is no direct evidence for the susceptibility of man. In the absence of such evidence, which could be obtained only by epidemiological studies, an attempt has been made to get indirect evidence by studying the metabolism of dimethylnitrosamine by human liver slices in vitro because it seems probable that this compound requires metabolic conversion to form an active carcinogenic intermediate. Dimethylnitrosamine is demethylated in the body to products which are further oxidized to carbon dioxide. One of these products is an alkylating intermediate which methylates cellular components including nucleic acids and proteins. DNA and RNA are methylated predominantly on guanine to yield 7-methylguanine, other sites being alkylated considerably less5. The significance of nucleic acid alkylation in cellular injury and carcinogenesis by nitrosamines has been discussed1,6.