Effect of dimethylnitrosamine on persistence of methylated guanines in rat liver and kidney DNA

Abstract

DIMETHYLNITROSAMINE is a potent carcinogen in many species, inducing tumours of the liver, kidney and lung^1,2. It is now well established that the carcinogenic activity of this compound is caused by its metabolic transformation within susceptible tissues to a chemically reactive agent which methylates a variety of cellular macromolecules^1–3. In spite of the fact that metabolism of dimethylnitrosamine is eight times greater in the liver than in the kidney, thus the alkylation of macromolecules is eight times greater in liver than kidney, a single large dose of dimethylnitrosamine given to the adult rat induces tumours of the kidney but not of the liver^1,4. (Liver tumours are produced in the adult rat only if dimethylnitrosamine is given after partial hepatectomy⁵ or by repeated small doses or prolonged feeding^1,2.) Similar experiments with certain nitrosamides have shown that although they penetrate and subsequently react to alkylate cellular components to a similar extent in many tissues, they do not produce an equal incidence of tumours in all these organs^1–4. It seems therefore, that different tissues vary quantitatively in their inherent susceptibility to these carcinogens. We report here results which may provide an explanation for this difference and also for the observation that large doses of dimethylnitrosamine are carcinogenic to the kidney while small doses are not.