Abstract
A high level of Cyp2a-5 was found in spontaneous and transplanted mouse hepatomas compared with normal liver. Increased expression of Cyp2a-5 was associated with an increase in coumarin 7-hydroxylation, a marker activity of Cyp2a-5, and the corresponding mRNA, suggesting that regulation of Cyp2a-5 in hepatomas is pretranslational. In contrast, the total P450 content and arylhydrocarbon hydroxylase and amidopyrene demethylase activities decreased. Pyrazole, a strong inducer of Cyp2a-5 in normal mouse livers, also increases this isozyme in hepatomas. A parallel increase in the corresponding mRNA suggests that pyrazole, like the formation of hepatomas, affects the regulation of Cyp2a-5 pretranslationally.
MeSH terms
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Aminopyrine N-Demethylase / metabolism
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Animals
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Aryl Hydrocarbon Hydroxylases / metabolism
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Blotting, Western
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Carbon Tetrachloride / toxicity
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Cytochrome P-450 CYP2A6
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Cytochrome P-450 Enzyme System / biosynthesis*
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Cytochrome P-450 Enzyme System / isolation & purification
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Cytochrome P-450 Enzyme System / metabolism*
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Gene Expression
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Isoenzymes / biosynthesis*
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Isoenzymes / metabolism
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Liver Neoplasms, Experimental / chemically induced
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Liver Neoplasms, Experimental / enzymology*
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Mice
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Mice, Inbred C3H
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Mice, Inbred CBA
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Mice, Inbred Strains
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Microsomes, Liver / enzymology*
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Mixed Function Oxygenases / biosynthesis*
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Mixed Function Oxygenases / isolation & purification
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Mixed Function Oxygenases / metabolism
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Pyrazoles / toxicity
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RNA, Messenger / biosynthesis
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RNA, Messenger / metabolism
Substances
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Isoenzymes
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Pyrazoles
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RNA, Messenger
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pyrazole
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Cytochrome P-450 Enzyme System
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Carbon Tetrachloride
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Mixed Function Oxygenases
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Aryl Hydrocarbon Hydroxylases
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Cytochrome P-450 CYP2A6
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Aminopyrine N-Demethylase