标题：Identification of four trans-3,4-dihydrodiol metabolites of 7,12-dimethylbenz[a]anthracene and their in vitro DNA-binding activities upon further metabolism
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1978
卷号：75
期号：11
页码：5466-5470
DOI：10.1073/pnas.75.11.5466
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
