The effects of inducing agents on cytochrome P450 and UDP-glucuronyltransferase activities in human HEPG2 hepatoma cells.
Selective induction in vitro of cytochrome P450-dependent mixed-function oxidase (MFO) and UDP-glucuronyltransferase (GT) activities was observed in the human HepG2 hepatoma cell line. 1,2-Benzanthracene (BA) induced MFO O-dealkylation activities for ethoxyresorufin, methoxyresorufin and benzyloxyresorufin, whereas phenobarbitone (PB) selectively induced pentoxyresorufin O-dealkylation and rifampicin (RIF) selectively induced benzyloxyresorufin O-dealkylation. Antibody inhibition experiments indicated that ethoxyresorufin and methoxyresorufin O-dealkylations were catalysed mainly by the P450 1A subfamily in untreated and BA-induced HepG2 cells, that additional unidentified P450 forms were considerably involved in methoxyresorufin and benzyloxyresorufin O-dealkylations and that the P450 2B subfamily was partially responsible for pentoxyresorufin O-dealkylation in PB-induced cells. Bilirubin GT activity was induced by PB, BA, RIF and dexamethasone, but 1-naphthol, morphine and testosterone GT activities were not induced by any of these treatments.
Department of Medicine and Therapeutics, University of Aberdeen, U.K.
H
H
Doostdar
M H
MH
Grant
W T
WT
Melvin
C R
CR
Wolf
M D
MD
Burke
D001551:Benz(a)Anthracenes / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D001551:Benz(a)Anthracenes; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; C030935:benz(a)anthracene; D006899:Mixed Function Oxygenases; D014453:Glucuronosyltransferase; D012293:Rifampin; D010634:Phenobarbital