Trans-3,4-dihydrodiols of 7,12-dimethylbenz[ajanthracene (7,, and 7,1di(hydroxymethyl)benia anthracene [7,12.(OHMe)2BAj have been identified as metabolites of the potent carcinogenic and adrenocorticolytic agent 7,12-Me BA. The four trans-3,4dihydro-diols 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-dihyarodiols of 7,12-Me2BA, 7-Me-12-OHMeBA, and 7-OHMe-12-MeBA were found to give rise to products that bind more strongl 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. 7,12-Dimethylbenz[a]anthracene (7,) is a potent inducer of mammary cancer (1) and causes adrenal apoplexy and massive necrosis in the two inner zones of the adrenal cortex (2) in rats. It is also known to be a transplacental carcinogen in rats (3), an inducer of hepatomas in mice (4) and nephroblastomas in ovariectomized rats (5), and a potent skin carcinogen in mice (6, 7). Metabolic activation by the microsomal enzyme systems is required for polycyclic aromatic hydrocarbons to exert their biological properties (refs. 8-10, and references given in refs. 9 and 10). It is known that 7,12-Me2BA can be metabolized to 7-OHMe-12-MeBA, 7-Me-12-OHMeBA, and 7,12-(OHMe)2BA as well as some dihydrodiol and phenolic derivatives (8,(11)(12)(13)(14)(15)(16) 7,7, 4-OH-7,12-(OHMe)2BA, 4-hydroxy-7,12-(OHMe)2BA; other phenolic and dihydrodiol metabolites are similarly abbreviated; HPLC, high-pressure liquid chromatography; m/e, mass-to-charge ratio.
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