Bacterial Mutagenicity of New Cyclopenta-Fused Cata-Annelated Polycyclic Aromatic Hydrocarbons, and Identification of the Major Metabolites of Benz(j)Acephenanthyrylene Formed by Aroclor-Treated Rat Liver Microsomes

摘要

Three novel cyclopenta-fused polycyclic aromatic hydrocarbons, benz(d)aceanthrylene, benz(k)aceanthrylene, and benz(j)acephenanthrylene, were synthesized and evaluated for mutagenic activity in the Ames Salmonella typhimurium plate incorporation assay. The two benzoaceanthrylene derivatives were active at low S9 concentrations in strain TA98 (4 and 27 rev/nmole respectively), as had been predicted from the calculated Delta deloc/B values of the carbocations derived from opening of the cyclopenta-fused epoxide rings, but the majority of this mutagenicity appeared to be due to free-radical decomposition products of spontaneous endo peroxide formation. These compounds were, therefore, not further investigated. Benz(j)acephenanthrylene was also an indirect-acting frameshift mutagen (8-12 rev/nmole in strain TA98), but unlike most of the previously-assayed cyclopenta-fused polycyclic aromatic hydrocarbons, exhibited no peak of activity at low S9 protein concentration. Consideration of the reduced activity of this compound compared to the related structure chrysene, the S9 dependence curves, and the predicted Delta deloc/B values of the postulated active species, suggests that in contrast to most other cyclopenta-fused polycyclic aromatic hydrocarbons, bay region diol-epoxide formation plays a greater role than epoxidation of the cyclopenta-fused ring in the metabolic activation of benz(j)acephenanthrylene.(Copyright (c) 1989 Elsevier Science Publishers B.V.(Biomedical Division).)