Induction of P450 3A by ethylbenzene without altering RNA levels.
Rats were treated with a single intraperitoneal injection of ethylbenzene in corn oil and the effects on cytochrome P450 3A-dependent activities, immunoreactive protein levels and RNA levels were examined. Ethylbenzene increased both P450 3A-dependent 2 beta-hydroxylation of testosterone and immunoreactive protein levels. These levels were maximally induced by 24 hr and diminished thereafter. Despite the increase in P450 3A protein, neither P450 3A1 nor P450 3A2 mRNA levels were altered by treatment with the hydrocarbon. These results clearly demonstrate that this P450 isozyme can be induced by either translational activation or stabilization of P450 3A protein and are suggestive of an elevation of P450 3A2 levels.
Yuan
W
W
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans 70112-1393.
Cawley
G F
GF
Eyer
C S
CS
Backes
W L
WL
D000818:Animals; D001483:Base Sequence; D001555:Benzene Derivatives / Q000494:pharmacology*; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004790:Enzyme Induction; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats
D001555:Benzene Derivatives; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; C004912:ethylbenzene