Inducibility of ethoxyresorufin deethylase and UDP-glucuronosyltransferase activities in two human hepatocarcinoma cell lines KYN-2 and Mz-Hep-1

被引:6
作者
Abid, A [1 ]
Sabolovic, N [1 ]
Magdalou, J [1 ]
机构
[1] UNIV NANCY 1,CTR MED,URA CNRS 597,F-54000 NANCY,FRANCE
关键词
cytochrome P450; human hepatoma cell lines; inducibility; UDP-glucuronosyltransferase;
D O I
10.1007/BF00143361
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Two human hepatoma cell. lines, KYN-2 and Mz-Hep-1 were characterized in terms of glucuronidation capacity and inducibility of cytochrome P4501A1/1A2 and several UDP-glucuronosyl-transferases (UGTs). Cytochrome P4501A1/1A2 activity was measured using 7-ethoxyresorufin and that of UGTs with 16 different substrates. The effects of dimethyl sulfoxide (DMSO), beta-naphthoflavone, alpha-naphthoflavone, and rifampicin on these drug-metabolizing enzyme activities were studied. DMSO treatment increased in a dose-dependent manner the ethoxyresorufin O-deethylase (EROD) activity in KYN-2 cells, while an opposite effect was observed in Mz-Hep-1 cells. In KYN-2 cells, EROD was more responsive toward beta-naphthoflavone treatment in combination with DMSO. This activity was enhanced in Mz-Hep-1 cells more than 83 times by beta-naphthoflavone. The enhancement of EROD activity by DMSO and beta-naphthoflavone treatments of KYN-2 cells was abolished by alpha-naphthoflavone treatment. In Mz-Hep-1, only the inducing effect of beta-naphthoflavone was abolished by alpha-naphthoflavone treatment. Rifampicin treatment of KYN-2 cells reversed both the DMSO and beta-naphthoflavone effects on the EROD activity. Glucuronidation of steroids, bile acids, fatty acids and drugs was effective in KYN-2 and Mz-Hep-1 cells. Both 1-naphthol glucuronidation and the level of UGT1*6 protein detected by immunoblot and supporting this activity were lowered by DMSO treatment and increased by beta-naphthoflavone treatment in KYN-2 cells. In Mz-Hep-1 cells, DMSO and beta-naphthoflavone had no effect on 1-naphthol glucuronidation activity. DMSO, beta-naphthoflavone and rifampicin also affected the glucuronidation of various substrates supported by different UGT isoforms. These results indicate that KYN-2 and Mz-Hep-1 cells can be used as new in vitro models for the studies of drug metabolism and the regulation of the corresponding enzymes.
引用
收藏
页码:115 / 123
页数:9
相关论文
共 26 条
[21]   EXPRESSION AND ROLE OF THE HUMAN LIVER UDP-GLUCURONOSYLTRANSFERASE UGT1-ASTERISK-6 ANALYZED BY SPECIFIC ANTIBODIES RAISED AGAINST A HYBRID PROTEIN PRODUCED IN ESCHERICHIA-COLI [J].
OUZZINE, M ;
PILLOT, T ;
FOURNELGIGLEUX, S ;
MAGDALOU, J ;
BURCHELL, B ;
SIEST, G .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1994, 310 (01) :196-204
[22]   DISTRIBUTION OF CYTOCHROME-P450 ACTIVITIES TOWARDS ALKOXYRESORUFIN DERIVATIVES IN RAT-BRAIN REGIONS, SUBCELLULAR-FRACTIONS AND ISOLATED CEREBRAL MICROVESSELS [J].
PERRIN, R ;
MINN, A ;
GHERSIEGEA, JF ;
GRASSIOT, MC ;
SIEST, G .
BIOCHEMICAL PHARMACOLOGY, 1990, 40 (09) :2145-2151
[23]  
PRITCHARD M, 1994, MOL PHARMACOL, V45, P42
[24]  
RITTER JK, 1990, J BIOL CHEM, V241, P5879
[25]  
SATO K, 1993, ANN NY ACAD SCI, V417, P213
[26]  
YANO H, 1988, ACTA PATHOL JAPON, V38, P953