Induction of the hepatic microsomal and nuclear cytochrome P-450 system by hexachlorobenzene, pentachlorophenol, and trichlorophenol. Chem Biol Interact 28: 291-299

Department of Dermatology, University of Düsseldorf Moorenstr 5, 4000 Düsseldorf F.R.G..
Chemico-Biological Interactions (Impact Factor: 2.58). 01/1980; 28(2-3):291-9. DOI: 10.1016/0009-2797(79)90169-8
Source: PubMed


The application of hexachlorobenzene (HCB), pentachlorophenol (PCP) and 2,4,5-trichlorophenol (TCP) to female rats led to an induction of both the microsomal and the nuclear cytochrome P-450 system in the liver. The increase of th mixed-function hydroxylase activities examined (7-ethoxycoumarin deethylase, 7-ethoxyresorufin deethylase, NADPH-dependent cytochrome c reductase, aminopyrine demethylase, benzpyrene hydroxylase) did not correlate strictly with the cytochrome P-450 content. Depending on the inducers and the substrates used, the content and the activity of the cytochrome P-450 were essentially smaller in the nuclei than in the microsomes. It was striking that in the nuclei those activities (benzpyrene hydroxylase, 7-ethoxyresorufin deethylase, 7-ethoxycoumarin deethylase) were preferably induced which can be attributed to the methyl-cholanthrene-induced form of the cytochrome P-450 (cytochrome P-448). These results suggest, also in the light of findings of other authors, the induction of different species of cytochrome P-450 in the nuclei and microsomes.

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  • No preview · Article · Dec 1979 · Archives for Dermatological Research
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    ABSTRACT: The subcellular distribution of aryl-hydrocarbon hydroxylase, NADPH-cytochrome c reductase, NADH:cytochrome c reductase, and NADH:cytochrome b5 reductase activities in mouse liver was studied using the biochemical membrane markers microsomal glucose-6-phosphatase, mitochondrial cytochrome c oxidase, and plasma membrane 5′-nucleotidase. The rate of appearance of activity of 3-methylcholanthrene-induced aryl-hydrocarbon hydroxylase in the microsomes of C57BL/6N mice is more than twice as rapid as that in the nuclear envelope. The nuclear fraction contains less than 1% of the total cellular activities of the hydroxylase and all three reductases. All detectable basal activity of aryl-hydrocarbon hydroxylase in the nuclear fraction of control CS7BL/6N and DBA/2N and 3-methylcholanthrene-treated DBA/2N mice and all detectable activities of NADPH:cytochrome c, NADH: cytochrome c, and NADH:catochrome b5 reductase in the nuclear fraction of control and 3-methylcholanthrene-treated C57BL/6N and DBA/2N mice can be completely accounted for by the degree of microsomal fragment contamination (as assessed by the microsomal marker glucose-6-phosphatase). These data raise doubts about certain previous reports of ‘nuclear’ enzyme activities in which microsomal contamination was not taken into account. However, there is more induced activity of aryl-hydrocarbon hydroxylase in the nuclear fraction of 3-methylcholanthrene-treated C57BL/6N mice than can be accounted for by the degree of microsomal membrane contribution. The murine Ah locus is known to regulate the induction by certain polycyclic aromatic chemicals of numerous drug-metabolizing enzyme activities such as aryl-hydrocarbon hydroxylase associated with cytochrome P1-450. The expression of 3-methylcholanthrene-inducible hydroxylase in nuclear membranes, like that in microsomal membranes, thus appears to be controlled by the Ah regulatory gene.
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