Differential induction of human liver UDP-glucuronosyltransferase activities by phenobarbital-type inducers.
(1) UDP-glucuronosyltransferase (UDP-GT) activities and their inducibility were investigated in human liver microsomes from a "liver bank". (2) UDP-GT activities were differentially induced in liver microsomes from patients treated with the phenobarbital-type inducers phenytoin or pentobarbital. UDP-GT activity towards bilirubin was induced 3-fold. Enzyme activities towards paracetamol, benzo(a)pyrene-3,6-quinol, 4-methylumbelliferone and 1-naphthol were moderately induced and to similar extents (2-fold). In contrast, morphine and 4-hydroxybiphenyl glucuronidation were not significantly affected. Cytochrome P-450 dependent 7-ethoxycoumarin O-deethylase was increased 5-fold. (3) A human hepatoma cell line (Hep G2) was studied to obtain information on the inducibility of human UDP-GT activities by 3-methylcholanthrene-type inducers. UDP-GT activities towards benzo(a)pyrene-3,6-quinol and 1-naphthol were moderately but significantly induced by 3-methylcholanthrene-treatment of the cells (2-fold), whereas 7-ethoxyresorufin O-deethylase and 7-ethoxycoumarin O-deethylase were increased over 100- and 10-fold, respectively. (4) The results suggest the existence of differentially inducible UDP-GT isoenzymes in human liver. The findings may be useful as a guide to characterize human liver UDP-GT isoenzymes.
Bock
K W
KW
Department of Pharmacology and Toxicology, University of Göttingen, Federal Republic of Germany.
Bock-Hennig
B S
BS
D000082:Acetaminophen / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001580:Benzopyrenes / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D014453:Glucuronosyltransferase / Q000096:biosynthesis*; D006801:Humans; D006873:Hydroquinones / Q000378:metabolism; D006923:Hymecromone / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis*; D008113:Liver Neoplasms / Q000201:enzymology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D008875:Middle Aged; D009284:Naphthols / Q000378:metabolism; D010424:Pentobarbital / Q000494:pharmacology*; D010672:Phenytoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001580:Benzopyrenes; D006873:Hydroquinones; D007527:Isoenzymes; D009284:Naphthols; C029350:1-naphthol; D000082:Acetaminophen; D006923:Hymecromone; D008748:Methylcholanthrene; D010672:Phenytoin; C054191:benzo(a)pyrene-3,6-quinol; D014453:Glucuronosyltransferase; D010424:Pentobarbital; D001663:Bilirubin