BILIARY EXCRETION OF 3-METHYLCHOLANTHRENE AS CONTROLLED BY ITS METABOLISM

¹ Department of Pharmacology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York

The carcinogen, 3-methylcholanthrene (MC), is converted to polar metabolites by hepatic drug-metabolizing enzymes of the rat. After an i.v. injection of ³H-MC, radioactivity is readily recovered in the bile in the form of ³H-MC metabolites. Biliary excretion of ³H-MC metabolites is accelerated by pretreatment with inducers of drug metabolism (3,4-benzpyrene, phenobarbital) and retarded by pretreatment with inhibitors of drug metabolism (SKF 525A, piperonyl butoxide, metyrapone). These agents have a similar effect on the rate of appearance of ³-MC metabolites in the blood. If ³H-MC metabolites are injected, their rate of excertion is far greater than that seen after the injection of ³H-MC. This rate is not affected by inducers nor inhibitors of drug metabolism. The evidence supports the concept that metabolism is the rate-limiting step in the biliary excretion of ³H-MC.