Relationship between hydrocarbon structure and induction of P450: effect on RNA levels.
1. Exposure to simple aromatic hydrocarbons has been shown to induce P450-dependent activities and the expression of particular P450 isozymes in a manner related to the molecular structure of the inducing hydrocarbon. In an attempt to identify the structural relationship controlling P450 induction, the effect of hydrocarbon treatment on the RNA levels for specific P450 isozymes was examined. 2. Rats were treated with daily injections of hydrocarbons (benzene, toluene, ethylbenzene, n-propylbenzene, m- and p-xylene) for 3 days, and the effects on specific RNA levels were examined by Northern blot hybridization. 3. Although P4502B1 mRNA was not elevated after hydrocarbon treatment, a significant elevation in 2B2 mRNA was observed after exposure to the larger aromatic hydrocarbons, ethylbenzene and m-xylene. It is interesting to note that despite the substantial elevation of P4502B protein levels, only a small elevation of P4502B1 and 2B2 RNA was observed. 4. P4502C11 mRNA was only suppressed by ethylbenzene administration, despite the depression of 2C11 protein levels by several hydrocarbons. 5. P4501A1 mRNA was not detectable and 2E1 mRNA was not changed by any aromatic hydrocarbon treatment investigated in this study. 6. The data indicate that the levels of mRNA species for a number of P450 isozymes are differentially regulated by exposure to hydrocarbons, and that small changes in hydrocarbon size or isomeric structure can influence the levels of these mRNA species.
Yuan
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Department of Pharmacology and Stanley S. Scott Cancer Center, Louisiana State University Medical Center, New Orleans 70112, USA.
White
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Strobel
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Backes
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D000818:Animals; D001483:Base Sequence; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology*; D015152:Blotting, Northern; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D004790:Enzyme Induction; D006838:Hydrocarbons / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship
D001555:Benzene Derivatives; D006838:Hydrocarbons; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System