Action of transcription and translation inhibitors on the enhancement of drug hydroxylation and glucuronidation by 3-methylcholanthrene and phenobarbital

Abstract

1. 1. A single dose of both phenobarbital and 3-methylcholanthrene was able to induce microsomal mixed function oxidase complex and UDP glucuronyltransferase ( p-nitrophenol) in 24 hours in rat liver. The increases differed, however, in amplitude. 3-Methylcholanthrene enhanced both the aryl hydrocarbon hydroxylase and p-nitroanisole O-demethylase activities, and phenobarbital increased the 0-demethylation of p-nitroanisole without affecting aryl hydrocarbon hydroxylase activity. 2. 2. Actinomycin D, 0.4 mg./kg. of body weight, was not able to block the rise in mixed function oxidase activity, but it significantly inhibited the induction of UDP glucuronyltransferase caused by phenobarbital or 3-methylcholanthrene administration. The higher dose, 0–8 mg./kg., blocked the induction of both mixed function oxidase complex and UDP glucuronyltransferase totally. 3. 3. Cycloheximide (1 mg./kg.) was partially active in inhibiting the increase of both drug oxidation and glucuronidation; the induction caused by phenobarbital was almost totally blocked but that achieved by 3-methylcholanthrene was only slightly inhibited. 4. 4. The biosynthesis of mixed function oxidase complex and UDP glucuronyltransferase are suggested to be under separate control mechanisms.