COMPARATIVE STUDY OF INHIBITORY ACTION OF ETHIONINE, 8-AZAGUANINE, 6-MERCAPTOPURINE AND X- OR GAMMA-IRRADIATION ON THE INDUCTION OF THE HEPATIC DRUG-METABOLIZING ENZYMES BY PHENOBARBITAL OR PHENAGLYCODOL

Abstract

Effects of carcinostatic agents, such as ethionine, 8-azaguanine, 6-mercaptopurine and X- or gamma-irradiation, on the induction of the hepatic drug-metabolizing enzymes by phenobarbital or phenaglycodol were examined by using young albino rat. It was observed that ethionine completely inhibited the induction of the enzymes when it was administered 30 minutes before the inducers, but the inhibitory effect of ethionine was diminished when the administration of ethionine was delayed after the injection of the inducers. Ethionine did not directly inhibit the enzyme activity, therefore it was supposed that ethionine inhibits de novo biosynthesis of protein of the apoenzyme. Contrary to the effect of ethionine, 6-mercaptopurine and X- or gamma-irradiation hardly inhibited or did not inhibit the induction of the enzymes. The results suggested that the RNA which is responsible for biosynthesis of hepatic microsomal drug metabolizing enzymes may be of long active life.