Stimulation of hepatic drug-metabolizing enzymes by DDT, polycyclic hydrocarbons or phenobarbital in adrenalectomized or castrated mice

Abstract

Benzpyrene treatment in rats increases the hepatic microsomal aniline hydroxylase pH optimum from 7 to 8. In mice treated with benzpyrene, no such shift in pH optimum of aniline hydroxylase was observed. Further studies on hormonal regulation of ethylmorphine- N-demethylase, aniline and benzpyrene hydroxylase in mice indicated that adrenalectomy, castration or adrenalectomy plus castration do not lower the basal (“uninduced”) activities of these enzymes (in rat with similar operations, basal activities are lowered by 50–90% depending on the enzyme). Also the magnitude of stimulation of hepatic microsomal drug metabolizing enzymes (HMDME) by pretreatment of mice with DDT, benzpyrene, 3-MC or phenobarbital in mice without adrenals, testes or both was not less than in sham-operated control mice (as occurs in rats), but instead was somewhat higher. These findings suggest that rats and mice differ in hormonal regulations of basal activities of HMDME and in the response of HMDME in animals pretreated with inducers of HMDME.