Decrease of cytochrome P-450 having arylhydrocarbon hydroxylase and increase of UDP-glucuronyltransferase glucuronizing phenolic xenobiotics in rat liver nodule.
Microsomal arylhydrocarbon (benzo[a]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/B[a]P, which is a form of cytochrome P-450 catalyzing benzo[a]pyrene hydroxylation in liver microsomes of untreated rats, it was shown that P-450/B[a]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/B[a]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 benzo[a]pyrene hydroxylase activity and increased UDP-glucuronyltransferase activity toward phenolic xenobiotics result from the decrease of the P-450 corresponding to P-450/B[a]P and the increase of the GT corresponding to GT-1.
Yokota
H
H
Department of Veterinary Biochemistry, School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan.
Ohgiya
N
N
Yuasa
A
A
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D000818:Animals; D001579:Benzopyrene Hydroxylase / Q000187:drug effects / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000187:drug effects / Q000378:metabolism*; D006965:Hyperplasia; D015151:Immunoblotting; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010636:Phenols / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D010636:Phenols; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene; D001579:Benzopyrene Hydroxylase; D014453:Glucuronosyltransferase