Induction of hepatic cytosolic DT diaphorase in rats treated with trans—stilbene oxide

Abstract

The flavoprotein DT diaphorase (NAD(P)H:oxidoreductase, EC 1.6.99.2) is a highly dicoumarolsensitive enzyme catalyzing the oxidation of NADH and NADPH by various quinones and redox dyes [l-3]. The physiological electron acceptor for DT diaphorase has not yet been established. However, it has been suggested that the enzyme serves as a quinone reductase in connection with conjugation of hydroquinones during detoxification, as well as in biosynthetic processes such as the vitamin K-dependent y-carboxylation of glutamyl residues in prothrombin synthesis (reviewed [3]). Treatment of rats with polycyclic aromatic hydrocarbons, potent inducers of the aryl hydrocarbon monooxygenase system [4,5], is known to increase hepatic DT diaphorase [6-l 11. The induction of DT diaphorase is due to an increase in the amount of the enzyme [ 121. The coinduction of DT diaphorase and aryl hydrocarbon monooxygenase [3,9] has drawn attention to a possible linkage between the genetic regulation of these activities. truns8tilbene oxide has been suggested to represent a new class of inducers of drug-metabolizing enzymes in the rat [ 13-161. This compound preferentially induces epoxide hydratase [ 13-161 and glutathione S-transferases [ 161, whereas cytochrome P450 linked monooxygenase reactions are only moderately affected [ 13-171. Because of the speci-