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Molecular Pharmacology

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Research ArticleArticle

Studies on the Enzymic Hydroxylation of 3,4-Benzpyrene

DONALD A. SILVERMAN and PAUL TALALAY
Molecular Pharmacology January 1967, 3 (1) 90-101;
DONALD A. SILVERMAN
Department of Pharmacology and Experimental Therapeutics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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PAUL TALALAY
Department of Pharmacology and Experimental Therapeutics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Abstract

We have investigated the relationship between the capacity of rat liver microsomal preparations to metabolize several foreign substances, and their content of the carbon monoxide-binding pigment, P-450. A rapid and convenient radioactive assay for the hydroxylation of 3,4-benzpyrene has been developed and the kinetics of this system studied. Optically clear, but not soluble, enzyme preparations were obtained by treatment of rat liver microsomes derived from benzpyrene-treated animals with the nonionic detergent Triton N-101. It was shown that the capacity of these preparations to hydroxylate 3,4-benzpyrene after various types of treatments, was impaired in direct proportion to the conversion of P-450 to its inactive form, P-420. Benzpyrene hydroxylase activity and the content of P-450 during storage were conserved to a large degree by the addition of glycerol to the medium. Treatment of rats with either 3,4-benzpyrene or phenobarbital resulted in elevated levels of benzpyrene hydroxylase, zoxazolamine hydroxylase, and p-nitroanisole demethylase activities as well as in a higher P-450 content, although the increases of these various components resulting from drug treatment were not in the same proportion. Evidence for the reactivation of acid-treated enzyme preparations by the addition of flavins was obtained.

ACKNOWLEDGMENT These studies have been supported in part by grants from the United States Public Health Service (Research Grant AM 07422 and Training Grant GM 1183).

  • Copyright ©, 1967, by Academic Press Inc.

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Molecular Pharmacology
Vol. 3, Issue 1
1 Jan 1967
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Research ArticleArticle

Studies on the Enzymic Hydroxylation of 3,4-Benzpyrene

DONALD A. SILVERMAN and PAUL TALALAY
Molecular Pharmacology January 1, 1967, 3 (1) 90-101;

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Research ArticleArticle

Studies on the Enzymic Hydroxylation of 3,4-Benzpyrene

DONALD A. SILVERMAN and PAUL TALALAY
Molecular Pharmacology January 1, 1967, 3 (1) 90-101;
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