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MORPHOLOGICAL TRANSFORMATION AND DNA ADDUCT FORMATION BY BENZ[J]ACEANTHRYLENE AND ITS METABOLITES IN C3H1OT1/2CL8 CELLS: EVIDENCE FOR BOTH CYCLOPENTA-RING AND BAY REGION METABOLIC ACTIVATION PATHWAYS
Nesnow, S., J. Lasley, S. Curti, J. Ross, G. Nelson, R. Sangaiah, AND A. Gold. MORPHOLOGICAL TRANSFORMATION AND DNA ADDUCT FORMATION BY BENZ[J]ACEANTHRYLENE AND ITS METABOLITES IN C3H1OT1/2CL8 CELLS: EVIDENCE FOR BOTH CYCLOPENTA-RING AND BAY REGION METABOLIC ACTIVATION PATHWAYS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-92/062.
Benz[j]aceanthrylene (B[j]A), a cyclopenta-fused polycyclic aromatic hydrocarbon (CP-PAH) related to 3-methylcholanthrene, has been studied to identify the major routes of metabolic activation in transformable C3H1OT1/2CLB (C3H1OT1/2) mouse embryo fibroblasts in culture. he morphological transforming activities of three potential intermediates formed by metabolism of B[j]A by C3H1OT1/2 cells, 9,10-dihydro-9,10-dihydroxy-B[j]A-7,8-oxide(B[j]A-diol-epoxide), B[j]A-9,10-oxide, and B[J]A-1,2-oxide as well as the two B[j]A-dihydrodiols were examined. B[j]A-diol-epoxide, B[J]A1,2-oxide, and B[j]A-9,10-diol were found to have moderate to strong activity with B[j]A-diol-epoxide the most active, giving a concentration response curve similar to B[j]A itself. [j]A-1,2-diol was found to be an extremely weak transforming agent. NA adducts of B[j]A, B[j]A1,2-diol, B[j]A-9,10-diol, B[j]A-diol-epoxide, B[j]A-9,10-oxide, and B[j]A-1,2-oxide in CH31OT1/2 cells were isolated, separated, identified, and quantitated using the 32P-postlabeling method. Qualitative and quantitative analysis of the postlabeling data suggests that B[j]A is metabolically activated by two distinct routes, the bay-region diol-epoxide route and the cyclopenta-ring oxide route, the former being the most significant.