Morphological Transformation and DNA Adduct Formation by Benz(j)aceanthrylene and Its Metabolites in C3H10T1/2CL8 Cells: Evidence for Both Cyclopenta-Ring and Bay-Region Metabolic Activation Pathways

摘要

Benz(j)aceanthrylene (B(j)A), a cyclopenta-fused polycyclic aromatic hydrocarbon related to 3-methylcholanthrene, has been studied to identify the major routes of metabolic activation in transformable C3H10T1/2CL8(C3H10T1/2) mouse embryo fibroblasts in culture. Previous studies have reported that the major (55% of total) B(j)A metabolite formed by C3H10T1/2 cells was (+ or -)-trans-9,10-dihydroxy-B(j)A(B(jA-9,10-diol), the dihydrodiol in the bay-region ring, with moderate amounts (14% of total) of (+ or -)-trans-1,2-dihydro-1,2-dihydroxy-B(j)A (B(j)A-1,2-diol), the cyclopenta-ring dihydrodiol. 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.