The in vivo induction of rat hepatic cytochrome P450-dependent enzyme activities and their maintenance in culture.
Cytochrome P450-dependent enzyme activities were measured in hepatocytes from adult male rats, induced in vivo with phenobarbitone, beta-naphthoflavone, dexamethasone or isoniazid: the stability of the induced activities in culture was also determined. Each inducer produced a characteristically different pattern of enzyme activities with dexamethasone, isoniazid and beta-naphthoflavone selectively inducing erythromycin N-demethylase, p-nitrophenol hydroxylase and ethoxyresorufin O-dealkylase respectively. In general, the induced activities were maintained for 24 hr in culture. This indicates the feasibility of an in vivo induction-hepatocyte culture system for the study of metabolism-mediated toxicity.
Hammond
A H
AH
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
Fry
J R
JR
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001571:Benzoflavones / Q000494:pharmacology; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1; D019392:Cytochrome P-450 CYP2E1; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D007538:Isoniazid / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D010088:Oxidoreductases / Q000096:biosynthesis; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D019324:beta-Naphthoflavone; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D007538:Isoniazid; D010634:Phenobarbital