EFFECTS OF ETHANOL, DEXAMETHASONE AND RU-486 ON EXPRESSION OF CYTOCHROMES-P450 CYTOCHROME-2B, CYTOCHROME-2E, CYTOCHROME-3A AND GLUTATHIONE TRANSFERASE-PI IN A RAT HEPATOMA-CELL LINE (FAO)

被引:35
作者
DEWAZIERS, I
BOUGUET, J
BEAUNE, PH
GONZALEZ, FJ
KETTERER, B
BAROUKI, R
机构
[1] INSERM U 75, CHU-Necker, Paris
[2] INSERM U 99, Hôpital Henri Mondor, Créteil
[3] Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, MD
[4] University College, London
来源
PHARMACOGENETICS | 1992年 / 2卷 / 01期
关键词
D O I
10.1097/00008571-199202000-00003
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The aim of our study was to investigate the suitability of Fao cells, derived from the Reuber H35 rat hepatoma as a tool for studying regulation of drug-metabolizing enzymes and drug metabolism. Fao cells express P450 2B, 2E, 3A and GST pi and were used to study the effects of different inducers on these enzymes. Ethanol considerably increased the amounts of P450 2E and, to a lesser extent, P450 2B and GST pi mRNA and protein. Dexamethasone decreased the amounts of P450 2B, 3A and GST pi mRNAs, but had no appreciable effect per se upon the protein concentration of these enzymes. However, it antagonized the induction of P450 2E, 2B and GST pi by ethanol, even at the protein level. RU 486 decreased P450 2B protein and P450 2E mRNA and protein levels without effecting P450 3A and GST pi expression. RU 486 did not antagonize the dexamethasone effects, suggesting that at least some of these effects are not mediated by the glucocorticoid receptor. These data indicate that these cells constitute a suitable tool for studying the regulation of drug-metabolizing enzyme expression and drug metabolism.
引用
收藏
页码:12 / 18
页数:7
相关论文
共 31 条
[1]  
Abramovitz M., Ishigari S., Litowsky I., Differential regulation of glutathione S-transferases in cultured hepatocytes, Hepatology, 9, pp. 235-239, (1989)
[2]  
Barouki R., Perrot N., Bouguet J., Chobert M.N., Toffis V., Pave-Preux M., Yang C.S., Beaune P., Hanoune J., Glucocorticoid hormones prevent the induction of y -glutamyl transpeptidase by ethanol in a rat hepatoma cell line, Biochem Pharmacol, 38, pp. 677-684, (1989)
[3]  
Chasserot-Golaz S., Beck G., Venetianer A., Corcos L., Effect of phenobarbital on the glucocorticoid receptor in rat hepatoma cells, Biochem Pharmacol, 40, pp. 1815-1819, (1990)
[4]  
Chasserot-Golaz S., Ribiero V., Genot G.L., Lechner M.C., Beck G., The steroid antagonist RU 38486 is metabolized by the liver microsomal P450 mono-oxygenases, Biochem Biophys Res Common, 67, pp. 1271-1278, (1990)
[5]  
Chirgwin J.M., Przybyla A.E., Macdonald R.J., Rutter W.J., Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease, Biochemistry, 18, pp. 5294-5299, (1979)
[6]  
Chobert M.N., Barouki R., Finidori J., Aggerbeck M., Hannoune J., Philibert D., Deraedt R., Antiglucocorticoid properties of RU 38486 in a differentiated hepatoma cell line, Biochem Pharmacol, 32, pp. 3481-3483, (1983)
[7]  
Corcos L., Rousset J.-P., Phenobarbital induces cytochrome P-450 mRNAs and enhance aflatoxin B1 toxicity in rat hepatoma cells, Guillouzo A, Ed, 164, pp. 445-449, (1988)
[8]  
Corcos L., Weiss M.C., Phenobarbital, dexamethasone and benzanthracene induce several cytochrome P450 mRNAs in rat hepatoma cells, PEBS Lett, 233, pp. 37-40, (1988)
[9]  
Deschartrette J., Weiss M.C., Characterization of differentiated and dedifferentiated clones from a rat hepatoma, Biochimie, 56, pp. 1603-1611, (1974)
[10]  
Donato M.T., Gomez-Lechon M.J., Castell J.V., Effect of xenobiotics on monooxygenase activities in cultured human hepatocytes, Biochem Pharmacol, 39, pp. 1321-1326, (1990)