Identification of Four Trans-3,4-dihydrodiol Metabolites of 7,12-dimethylbenz[a]anthracene and Their in Vitro DNA-binding Activities Upon Further Metabolism

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1978 Nov 1

PMID 103094

Citations 6

Authors

M W Chou

S K Yang

Affiliations

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Abstract

Trans-3,4-dihydrodiols of 7,12-dimethylbenz[a]anthracene (7,12-Me2BA), 7-methyl-12-hydroxymethylbenz[a]anthracene (7-Me-12-OHMeBA), 7-hydroxymethyl-12-methylbenz[a]anthracene (7-OHMe-12-MeBA), and 7,12-di(hydroxymethyl)benz[a]anthracene [7,12-(OHMe)2BA] have been identified as metabolites of the potent carcinogenic and adrenocorticolytic agent 7,12-MeBA. The four trans-3,4-dihydrodiols were identified by their (i) ultraviolet-visible absorption and fluorescence properties, (ii) different retention times on both reversed-phase and normal-phase high-pressure liquid chromatography, (iii) mass spectral analysis, and (iv) inability to form vicinal cis-acetonides. Upon further metabolism by liver microsomes, the trans-3,4-dihydrodiols of 7,12-Me2BA, 7-Me-12OHMeBA, and 7-OHMe-12-MeBA were found to give rise to products that bind more strongly to DNA in vitro than do the products of 7,12-Me2BA. The evidence suggests that one or more of the four trans-3,4-dihydrodiols may be the proximate carcinogenic and adrenocorticolytic metabolites.

Citing Articles

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Metabolism of 7,12-dimethylbenz[a]anthracene by Cunninghamella elegans.

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Differentiation of the mammary gland and susceptibility to carcinogenesis.

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Stereoselective fungal metabolism of 7,12-dimethylbenz[a]anthracene: identification and enantiomeric resolution of a K-region dihydrodiol.

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Quantitative predictability of carcinogenicity of the covalent binding index of chemicals to DNA: comparison of the in vivo and in vitro assays.

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