The degradation of 7,12-dimethylbenz[a]anthracene (DMBA), a carcinogenic polycyclic aromatic hydrocarbon, by cultures of Mycobacterium vanbaalenii PYR-1 was studied. When M. vanbaalenii PYR-1 was grown in the presence of DMBA for 136 h, high-pressure liquid chromatography (HPLC) analysis showed the presence of four ethyl acetate-extractable compounds and unutilized substrate. Characterization of the metabolites by mass and nuclear magnetic resonance spectrometry indicated initial attack at the C-5 and C-6 positions and on the methyl group attached to C-7 of DMBA. The metabolites were identified as cis-5,6-dihydro-5,6-dihydroxy-7,12-dimethylbenz[a]anthracene (DMBA cis-5,6-dihydrodiol), trans-5,6-dihydro-5,6-dihydroxy-7,12-dimethylbenz[a]anthracene (DMBA trans-5,6-dihydrodiol), and 7-hydroxymethyl-12-methylbenz[a]anthracene, suggesting dioxygenation and monooxygenation reactions. Chiral stationary-phase HPLC analysis of the dihydrodiols showed that DMBA cis-5,6-dihydrodiol had 95% 5S,6R and 5% 5R,6S absolute stereochemistry. On the other hand, the DMBA trans-5,6-dihydrodiol was a 100% 5S,6S enantiomer. A minor photooxidation product, 7,12-epidioxy-7,12-dimethylbenz[a]anthracene, was also formed. The results demonstrate that M. vanbaalenii PYR-1 is highly regio-and stereoselective in the degradation of DMBA.7,12-Dimethylbenz[a]anthracene (DMBA) is a potent carcinogen in rodent skin and mammary cells (7). Alkylated benz[a]-anthracenes are formed in sediments by thermal processes and have also been identified in cigarette smoke condensate, coal gasification and stock gas particulates, and roofing tar extracts (1, 10). Studies from several laboratories have indicated that DMBA is bioactivated by various isoforms of mammalian cytochrome P-450 and epoxide hydrolase to form DMBA-3,4-dihydrodiol-syn-and anti-1,2-epoxides that react with DNA to form adducts that lead to tumor initiation (22,32,33). An alternative mechanism for metabolic activation is hydroxylation of the alkyl side chain to form hydroxymethyl derivatives, followed by sulfotransferase-catalyzed activation of DMBA to form electrophilic sulfuric acid esters that bind to DNA (6). 7,12-Dimethylbenz[a]anthracene has been used as a model polycyclic aromatic hydrocarbon (PAH) in the following ways: (i) as a tumor initiator or as a complete carcinogen in rodent skin and mammary gland models of carcinogenesis (15, 22), (ii) as a prototype methyl-substituted PAH in mutation and cancer research (15), (iii) to determine whether metabolic activation occurs via bay-region dihydrodiol epoxide metabolites or hydroxylation of the methyl substituent with subsequent formation of electrophilic sulfuric acid esters (6), and (iv) to determine the environmental fate of methyl-substituted PAHs.In contrast to the numerous studies of the metabolism, DNA adduct formation, and tumor induction by DMBA in mammalian cells, little is known about the microbial metabolism of this potent carcinogen. Several strains of fungi metabolize methylbenz [a]anthracenes at the methyl group, with furth...