Some effects of 3-methylcholanthrene on uridine diphosphate glucuronyltransferase in the rat and guinea pig

Abstract

Treatment of young rats and guinea pigs with 3-methylcholanthrene significantly increased liver microsomal glucuronyltransferase activity. The earliest detectable increase in rat glucuronyltransferase activity occurred between 6 and 12 hr following administration of the polycyclic hydrocarbon, and after 48 hr, glucuronyltransferase activity in treated animals was twice that in control animals. Liver glucuronyltransferase activity was not effected when rats were pretreated with nikethamide, chlorcyclizine or phenobarbital. Administration of d, l-ethionine or actinomycin D, inhibitors of protein synthesis, prevented the increase in glucuronyltransferase activity following 3-methylcholanthrene administration. Kinetic analysis of glucuronyltransferase activity indicated that the V max was significantly increased in treated rats and guinea pigs. The K m of the enzyme from 3-methylcholanthrene treated rats was significantly decreased, whereas, the K m of the enzyme from treated guinea pigs was significantly increased. These changes in V max and K m suggest that induction of glucuronyltransferase by 3- methylcholanthrene may involve qualitative as well as quantitative changes in the enzyme.