THE EFFECTS OF INDUCING AGENTS ON CYTOCHROME-P450 AND UDP-GLUCURONOSYLTRANSFERASE ACTIVITIES IN HUMAN HEPG2 HEPATOMA-CELLS

被引：71
作者：
DOOSTDAR, H
GRANT, MH
MELVIN, WT
WOLF, CR
BURKE, MD
机构：
[1] UNIV ABERDEEN MARISCHAL COLL, DEPT BIOMED SCI, ABERDEEN AB9 1AS, SCOTLAND
[2] UNIV ABERDEEN, DEPT MED & THERAPEUT, ABERDEEN AB9 1AS, SCOTLAND
[3] UNIV ABERDEEN, DEPT BIOCHEM, ABERDEEN AB9 1AS, SCOTLAND
[4] UNIV EDINBURGH, ICRF LAB, EDINBURGH EH8 9XD, SCOTLAND
来源：
BIOCHEMICAL PHARMACOLOGY | 1993年 / 46卷 / 04期
基金：
英国惠康基金;
关键词：
D O I：
10.1016/0006-2952(93)90548-B
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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.
引用
收藏
页码：629 / 635
页数：7
相关论文
共 48 条
[1]  
BOCK KW, 1984, DRUG METAB DISPOS, V12, P93
[2]   DIFFERENTIAL INDUCTION OF HUMAN-LIVER UDP-GLUCURONOSYLTRANSFERASE ACTIVITIES BY PHENOBARBITAL-TYPE INDUCERS [J].
BOCK, KW ;
BOCKHENNIG, BS .
BIOCHEMICAL PHARMACOLOGY, 1987, 36 (23) :4137-4143
[3]   EFFECT OF RIFAMPICIN TREATMENT ON METABOLISM OF ESTRADIOL AND 17 ALPHA-ETHINYLESTRADIOL BY HUMAN LIVER-MICROSOMES [J].
BOLT, HM ;
KAPPUS, H ;
BOLT, M .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1975, 8 (05) :301-307
[4]  
BROCKMEYER N, 1985, BR J CLIN PHARM, V19, pP554
[5]   ETHOXYPHENOXAZONES, PENTOXYPHENOXAZONES, AND BENZYLOXYPHENOXAZONES AND HOMOLOGS - A SERIES OF SUBSTRATES TO DISTINGUISH BETWEEN DIFFERENT INDUCED CYTOCHROMES-P-450 [J].
BURKE, MD ;
THOMPSON, S ;
ELCOMBE, CR ;
HALPERT, J ;
HAAPARANTA, T ;
MAYER, RT .
BIOCHEMICAL PHARMACOLOGY, 1985, 34 (18) :3337-3345
[6]  
BURKE MD, 1983, CHEM-BIOL INTERACT, V45, P243
[7]  
DAUJAT M, 1991, METHOD ENZYMOL, V206, P345
[8]  
Del Villar E, 1974, Drug Metab Dispos, V2, P370
[9]   VARIATION IN DRUG-METABOLIZING ENZYME-ACTIVITIES DURING THE GROWTH OF HUMAN HEP G2 HEPATOMA-CELLS [J].
DOOSTDAR, H ;
DEMOZ, A ;
BURKE, MD ;
MELVIN, WT ;
GRANT, MH .
XENOBIOTICA, 1990, 20 (04) :435-441
[10]   THE INFLUENCE OF CULTURE-MEDIUM COMPOSITION ON DRUG-METABOLIZING ENZYME-ACTIVITIES OF THE HUMAN-LIVER DERIVED HEP-G2 CELL-LINE [J].
DOOSTDAR, H ;
DUTHIE, SJ ;
BURKE, MD ;
MELVIN, WT ;
GRANT, MH .
FEBS LETTERS, 1988, 241 (1-2) :15-18
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