Bacterial mutagenicity of new cyclopenta-fused cata-annelated polycyclic aromatic hydrocarbons, and identification of the major metabolites of benz[ j]acephenanthrylene formed by Aroclor-treated rat liver microsomes

Abstract

Three novel cyclopenta-fused polycyclic aromatic hydrocarbons were synthesized, benz[ d]aceanthrylene,benz[ k]aceanthrylene, and benz[ j] acephenanthrylene, and evaluated for mutagenic activity in the Ames Salmonella typhimurium plate incorporation assay. The two benzaceanthrylene derivatives were active at low S9 concentrations in strain TA98 (4 and 27 rev/nmole respectively), as had been predicted from the calculated ΔE deloc/ β 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. The principal metabolites formed from this compound by microsomes from Aroclor-treated rat liver were benz[ j]acephenanthrylene-4,5-dihydro-4,5-diol (necessarily derived from hydration of benz[ j]acephenanthrylene 4,5- oxide) and benz[ j]acephenanthrylene-9,10-dihydro-9,10-diol (precursor to benz[ j]acephenanthrylene-9,10-dihydrodiol 7,8-oxide, the bay-region diol-epoxide). Consideration of the reduced activity of this compound compared to the related structure chrysene, the S9 dependence curves, and the predicted ΔE deloc/ β 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.