Liver-enzyme induction in lindane- and captan-treated rats

Abstract

The effects of lindane and of captan on several liver-enzyme activities involved in the detoxication/activation of foreign chemicals was studied in male rats. The parameters selected were acid phosphatase as a marker of the lysosomal system involved in the cellular response to intoxication, azoreductase and p-nitroanisole- O-demethylase as detoxication enzymes, and the binding of benzo[ a]pyrene (BP) and dimethylaminoazobenzene metabolites to DNA as indicators of metabolic activation. The continuous feeding of diet containing 120 ppm lindane for 4 wk induced O-demethylase and BP-DNA binding (between two- and threefold), without affecting the other enzymes. BP-DNA binding was induced by as little as 24 ppm lindane. When lindane was given ip (3 × 20 mg/kg/day), induction of O-demethylase and benzo[ a]pyrene activation again occurred and there was also a decrease in acid phosphatase. A similar but more pronounced pattern was observed in rats treated with phenobarbital (3 × 80 mg/kg/day). Methylcholanthrene induced the three activities in the decreasing order: BP-DNA binding, O-demethylase and acid phosphatase. Ingestion of diet containing 10 or 50 ppm captan for 4 wk did not alter any enzymatic activities. Levels of 3000 or 15,000 ppm led to a significant (fourfold) induction in O-demethylase and BP-DNA binding, but did not affect acid phosphatase activity. Thus not only organochlorine pesticides but also others such as the phthalimide, captan, are potent inducers of the mixed-function oxidases. The route of administration, dose and duration of treatment are predominant factors in their effects on the balance of enzymes involved in the detoxication or activation of chemicals.