In vivo and in vitro induction of cytochrome P-450 synthesis in hyperoxia.
Exposure of dark- or light-adapted mice to 1--3 ATA oxygen for times ranging from 15 min to 4 h caused a progressive increase in P-450, which peaked and then decayed. The rate of decay appears to be independent of PO2. A linear, inverse relationship was noted between the PO2 in the range of 1--4 ATA and the duration of exposure needed to obtain maximum P-450 levels. Cytochrome P-450 was induced by hyperoxia in vitro in a suspension of hepatocytes, and this induction was prevented by inhibitors of transcription and translation and by disulfiram. Cytochrome P-450 induction is not a general phenomenon of stress, albeit physical restraint may decrease the level of P-450 induced. Induction was a specific effect of increased oxygen tensions and was not due to pressure per se. Neither equivalent pressures of compressed air in the in vivo experiments nor equivalent pressures of nitrogen in the in vitro experiments induced P-450. Induction in vivo was inhibited by disulfiram and metyrapone. Hyperoxia is the most rapid inducer of P-450 yet found, and this response may represent a protective mechanism against hyperoxia.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003623:Dark Adaptation; D004221:Disulfiram / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006931:Hyperbaric Oxygenation; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D013997:Time Factors
D003577:Cytochrome P-450 Enzyme System; D004221:Disulfiram