Bacterial mutagenicity of the three isomeric dicyclopenta-fused pyrenes: the effects of dicyclopenta topology.

Abstract Cyclopenta[ cd ]pyrene ( 1 ) and its congeners dicyclopenta[ cd,mn ]- ( 2 ), dicyclopenta[ cd,fg ]- ( 3 ), dicyclopenta[ cd,jk ]pyrene ( 4 ), which were all identified as constituents of combustion exhausts, as well as their partially hydrogenated derivatives 3,4-dihydrocyclopenta[ cd ]- ( 5 ), 1,2,4,5-tetrahydrodicyclopenta[ cd,mn ]- ( 6 ), 5,6,7,8-tetrahydrodicyclopenta[ cd,fg ]- ( 7 ) and 1,2,6,7-tetrahydrodicyclopenta[ cd,jk ]pyrene ( 8 ), were assayed for mutagenicity in the Salmonella typhimurium strain TA98 using different concentrations of microsomal protein in the metabolic activation system (S9-mix, with S9-fraction from liver of Aroclor-1254-treated rats: 2, 4 and 10% (v/v), respectively). Whereas a positive mutagenic response is found for 1 – 4 in the presence of S9-mix, 5 – 8 exert no mutagenicity either with or without S9-mix. Since for 1 – 4 the highest response is observed with S9-mix 2% (v/v) instead of the standard 4% (v/v), a one-step activation pathway, i.e. epoxidation of the five-membered ring olefinic bonds, appears to be operational. Surprisingly, 3 and, to a lesser extent, 2 (11.7 versus 4.2 His revertants/nmol) also give a positive response in the absence of S9-mix. Hence, 2 and 3 are expected to contribute to the direct-acting mutagenicity of the non-polar fraction of combustion exhausts. Presumably for the direct-acting mutagenicity one-electron transfer processes play a role in bioactivation. The experimental observations are supported by semi-empirical AM1 calculations on the possible ultimate metabolites, i.e. mono-epoxides ( 2a – 4a ), cis -di-epoxides ( 2b – 4b ) and trans -di-epoxides ( 2c – 4c ) and the related mono-hydroxy carbocations ( 2d – 4d and 2e – 4e ), and the radical anions 1 − – 4 − .