3-Methylcholanthrene Induction of Enzymes in the Vitamin K-dependent Carboxylation System

The effect of 3-methylcholanthrene on liver enzymes in the vitamin K-dependent carboxylation system has been investigated in normal rats and rats treated with the anticoagulant warfarin. It was found that 3-methylcholanthrene did not interfere with the anticoagulant function of the drug. Treatment of rats with 3-methylcholanthrene resulted in a 2.7-fold increase in liver cytosolic DT-diaphorase activity and a 1.5-fold increase in liver microsomal vitamin K-dependent carboxylase activity. A pathway for production of reduced vitamin K cofactor for the vitamin K-dependent carboxylase is catalyzed by DT-diaphorase and an as yet unidentified NADH-specific dehydrogenase(s). The data suggest that the unidentified enzyme(s) in the pathway is not induced by 3-methylcholanthrene.