Influence of pretreatment with various insecticides on the N-demethylation of dimethylnitrosamine

Abstract

The effects of various classes of insecticides were studied on the N-demethylation of dimethylnitrosamine (DMN) by mouse liver enzymes. Organochlorine insecticides, represented by lindane, DDT, and endrin, increased the activities of DMN demethylase I and II. The latter enzyme was more susceptible to the inducive action of the tested chlorinated insecticides. On the other hand, the synthetic pyrethroids, fenvalerate and flucythrinate, did not alter the activity of either enzyme. While pretreatment with carbaryl, a carbamate derivative, was without effect, moderate elevation in the activity of both demethylases was observed following administration of carbofuran. Dimethoate, representing organophosphorus compounds, was the only insecticide tested to inhibit the N-demethylation of DMN, with more pronounced effect on DMN demethylase I. Since DMN requires metabolic activation for its hepatotoxic and carcinogenic actions, alterations in the activities of its metabolizing enzymes as a sequela of exposure to certain insecticides may change susceptibility to its toxicity and/or carcinogenicity.