Metabolic Pathways of 7,12-dimethylbenz[a]anthracene in Hepatic Microsomes
- Creators
- Yang, Shen K.
- Dower, William V.
Abstract
High pressure liquid chromatography has enabled quantitative analysis of the in vitro metabolism of 7,12-dimethylbenz[a]anthracene, 7-methyl-12-hydroxymethylbenz[a]anthracene, 7-hydroxymethyl-12-methylbenz[a]anthracene, and 7,12-dihydroxymethylbenz[a]anthracene by 3-methylcholanthrene-induced and control rat liver microsomes. The following previously unrecognized metabolites have been tentatively identified: 5,6-dihydro-5,6-dihydroxy-7-methyl-12-hydroxymethylbenz[a]anthracene, 3-hydroxy-7,12-dihydrodihydroxymethylbenz[a]anthracene, 4-hydroxy-7,12-dihydrodihydroxymethylbenz[a]anthracene, and 8,9-dihydro-8,9-dihydroxy-7,12-dihydroxymethylbenz[a]anthracene. The epoxide hydratase inhibitor 1,2-epoxy-3,3,3-trichloropropane was found to eliminate all dihydrodiol formation and markedly inhibit the formation of several dimethylbenzanthracene metabolites. It is proposed that the tentatively identified 3-hydroxy and 4-hydroxy derivatives are formed by an enzymatic mechanism that does not involve epoxides as intermediates. The metabolic pathways of 7,12-dimethylbenz[a]anthracene in hepatic microsomal enzymes are proposed.
Additional Information
Copyright © 1975 by the National Academy of Sciences. Communicated by John D. Baldeschwieler, April 24, 1975. The authors gratefully acknowledge helpful discussions with Drs. John D. Baldeschwieler and Harry V. Gelboin. This work was supported by the National Science Foundation under Grant no. 38855X, and the National Institutes of Health under Grant no. GM-21111-02. S.K.Y. is the recipient of a Postdoctoral Research Fellowship (1-F-22-CA 01474-01) from the National Cancer Institute. This is Contribution no. 5037 from the Arthur Amos Noyes Laboratory.Files
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Additional details
- Eprint ID
- 10641
- Resolver ID
- CaltechAUTHORS:YANpnas75
- Created
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2008-05-22Created from EPrint's datestamp field
- Updated
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2019-10-03Created from EPrint's last_modified field