Bacterial mutagenicity of two cyclopentafused isomers of benzpyrene

Abstract

Two novel cyclopentafused polycyclic aromatic hydrocarbons, naphtho(1,2,3- mno)acephenanthrylene (cyclopenta benzo[ e]pyrene) and naphtho(2,1,8- hij)acephenanthrylene (cyclopenta( ij)benzo[a]pyrene) were evaluated for mutagenic activity in the Ames Salmonella typhimurium plate incorporation assay. Both compounds required S9 metabolic activation, and showed optimal activity at low S9 concentrations (below 0.6 mg/plate). Both compounds induced frameshift and base-pair substitution mutations, being active in strains TA98, TA100, TA1537, TA1538 and TA104, but not in strain TA1535. Cyclopenta( ij)benzo[ a]pyrene was more active than cyclopentabenzo[ e]pyrene, and both were more potent than their parent ring systems, benzo[ a]pyrene and benzo[ e]pyrene, respectively. Cyclopenta( ij)benzo[ a]pyrene was more active in strain TA104 than in TA100 or TA98 (250–470, 340 and 80–100 rev/nmole) as was benzo[ a]pyrene (120, 70 and 40 rev/nmole respectively); cyclopentabenzo[ e]pyrene was more active in TA100 than TA104 or TA98 (70 versus 50 and 40 rev/nmole), and benzo[ e]pyrene showed a similar pattern (4, 3.5 and 0.6 rev/nmole). The relative potencies of the four compounds are in accord with predictions based on perturbational molecular orbital calculations. The peak of activity at low S9 concentrations is consistent with epoxidation at the cyclopentafused ring being the major route of metabolic activation for both these cyclopentafused compounds.