Decrease of cytochrome P-450 having arylhydrocarbon hydroxylase and increase of UDP-glucuronyltransferase glucuronizing phenolic xenobiotics in rat liver nodule.

Microsomal arylhydrocarbon (benzoa]pyrene) hydroxylase activity in hyperplastic nodules in the livers of rats was decreased by feeding 2-acetylaminofluorene in their diet to 10% of that without 2-acetylaminofluorene feeding. By immunoblotting analysis with the antibodies raised against P-450/Ba]P, which is a form of cytochrome P-450 catalyzing benzoa]pyrene hydroxylation in liver microsomes of untreated rats, it was shown that P-450/Ba]P content was decreased in the microsomes prepared from the nodular tissues. Microsomal UDP-glucuronyltransferase activity toward phenolic xenobiotics such as 1-naphthol and 4-nitrophenol was increased by 4.5-5.0-fold in the nodular tissues. This increase was inhibited by the addition of antibodies raised against GT-1, a form of UDP-glucuronyltransferase glucuronizing phenolic xenobiotics. Immunoblotting analysis with the antibodies against GT-1 showed that a protein band corresponding to GT-1 was increased in the microsomes from nodular tissues. The increased UDP-glucuronyltransferase also had about 4,000 daltons "high mannose" oligosaccharide(s) like GT-1. The decreases of P-450/Ba]P and increases of GT-1 were observed mainly in nodular foci of the liver tissues. These results indicate that in liver nodules, decreased cytochrome P-450-dependent benzoa]pyrene hydroxylase activity and increased UDP-glucuronyltransferase activity toward phenolic xenobiotics result from the decrease of the P-450 corresponding to P-450/Ba]P and the increase of the GT corresponding to GT-1.