Studies in vivo on the Inhibition of Dimethylnitrosamine Metabolism in the Rat

Abstract

The results (Table 2) showed that sodium phenobarbitone pretreatment did not affect the metabolic rate in vivo of dimethylnitrosamine and the LDSo was unchanged. On the other hand, 20-methylcholanthrene treatment not only enhanced the metabolic rate of dimethylnitrosamine in uivo to 125% of the control, but also significantly increased the toxicity of dimethylnitrosamine in the young male rats. The results of our studies show that phenobarbitone and 20-methylcholanthrene induced hepatic dimethylnitrosamine demethylase activity in young and mature rats of both sexes. These findings are in agreement with thereported induction of dimethylnitrosamine demethylase activity in mice after the administration of polychlorinated biphenyls, compounds known to induce drug-metabolizing enzyme activity (Czygan et al., 1973). However, this inductive effect in vitro was not reflected in the metabolic rate of dimethylnitrosamine in the intact animal. Further, the toxicity of dimethylnitrosamine appeared to be influenced by the metabolism in uivo. Our findings question the relevance of hepatic dimethylnitrosamine demethylase activity as an index of the metabolism in uivo and the consequent toxicity of dimethylnitrosamine in the rat.