Identification of four trans-3,4-dihydrodiol metabolites of 7,12-dimethylbenz[a]anthracene and their in vitro DNA-binding activities upon further metabolism.
- 1 November 1978
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 75 (11), 5466-5470
- https://doi.org/10.1073/pnas.75.11.5466
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] were identified as metabolites of the potent carcinogenic and adrenocorticolytic agent 7,12-Me2BA. The 4 trans-3,4-dihydrodiols were identified by their UV-visible absorption and fluorescence properties, different retention times on both reversed-phase and normal-phase high-pressure liquid chromatography, mass spectral analysis and inability to form vicinal cis-acetonides. Upon further metabolism by rat liver microsomes, the trans-3,4-dihydrodiols of 7,12-Me2BA, 7-Me-12-OHMeBA and 7-OHMe-12-MeBA gave rise to products that bind more strongly to DNA in vitro than do the products of 7,12-Me2BA. Apparently 1 or more of the 4 trans-3,4-dihydrodiols may be the proximate carcinogenic and adrenocorticolytic metabolites.This publication has 37 references indexed in Scilit:
- High mutagenicity of metabolically activated chrysene 1,2 dihydrodiol: Evidence for bay region activation of chryseneBiochemical and Biophysical Research Communications, 1977
- High microsome-mediated mutagenicity of the 3,4-dihydrodiol of 7-methylbenz[a]anthracene in S. typhimurium TA 98Biochemical and Biophysical Research Communications, 1977
- COMPARISON OF TUMOR-INITIATING ACTIVITIES OF BENZO(A)PYRENE ARENE OXIDES AND DIOL-EPOXIDES1977
- Enzymatic conversion of benzo(a)pyrene leading predominantly to the diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene through a single enantiomer of r-7, t-8-dihydroxy-7,8-dihydrobenzo(a)pyrene.Proceedings of the National Academy of Sciences, 1976
- Exceptional mutagenicity of a benzo[a]pyrene diol epoxide in cultured mammalian cellsNature, 1976
- Chemical CarcinogenesisAnnual Review of Biochemistry, 1975
- METABOLISM OF POLYCYCLIC COMPOUNDS. THE METABOLISM OF 7,12-DIMETHYLBENZ[α]ANTHRACENE BY RAT-LIVER HOMOGENATESBiochemical Journal, 1965
- SELECTIVE ADRENAL NECROSIS AND APOPLEXY INDUCED BY 7,12-DIMETHYLBENZ(a)ANTHRACENEThe Journal of Experimental Medicine, 1961
- Mammary Cancer Induced by a Single Feeding of Polynuclear Hydrocarbons, and its SuppressionNature, 1961
- PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENTJournal of Biological Chemistry, 1951