INDUCTION OF HEPATIC DRUG-METABOLIZING-ENZYMES BY CHLORNITROFEN (CNP)AND CNP-AMINO IN RATS AND MICE

The induction of hepatic drug-metabolizing enzymes by chlornitrofen (C NP) and CNP-amino was studied in the liver of male rats and mice. CNP- amino increased the activities of 7-pentoxyresorufin O-depentylase (PR OD) and 7-benzyloxyresorufin O-debenzylase (BROD) as CYP2B1-dependent monooxygenase 3.6- and 4.1-fold in rats. On the contrary, these enzyme activities in mice were induced by CNP rather than by CNP-amino. Furt hermore, immunoblotting showed that the protein levels of CYP2B subfam ily cytochrome P450 (P450) in liver microsomes of rats and mice were i ncreased by CNP or CNP-amino. Phase II drug-metabolizing enzymes, UDP- glucuronyltransferase (UGT) and glutathione S-transferase (GST) levels in mice were also significantly increased from 1.4 to 2.5-fold by CNP or CNP-amino. However, neither CNP nor CNP-amino affected UGT and GST in rats. These results suggest that CNP and or CNP-amino induce the P 450 isoforms of CYP2B subfamily in the rat and mouse liver, and that t he inducibility of drug-metabolizing enzyme by the compounds is differ ent between rats and mice.