Effects of ethanol, dexamethasone and RU 486 on expression of cytochromes P450 2B, 2E, 3A and glutathione transferase pi in a rat hepatoma cell line (Fao).
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 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.
de Waziers
I
I
INSERM U 75, CHU-Necker, Paris, France.
Bouguet
J
J
Beaune
P H
PH
Gonzalez
F J
FJ
Ketterer
B
B
Barouki
R
R
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002460:Cell Line; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism; D051381:Rats
D015735:Mifepristone; D000431:Ethanol; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; C071207:1,2-dimethylhydrazine demethylase; D010089:Oxidoreductases, N-Demethylating; D005982:Glutathione Transferase