Mutagenic activity of nitro-substituted cyclopenta-fused polycyclic aromatic hydrocarbons towards Salmonella...

Cyclopenta-fused isomers of pyrene and benz[a]anthracene, nitrated on the etheno bridge, were synthesized and tested in the Ames plate-incorporation assay. Since enzymatic reduction, if it occurs in these compounds, would form arylhydroxylamines which in turn would form highly stabilized arylnitrenium ions, we hoped to test the hypothesis that the direct-acting mutagenic activity of nitroPAH is correlated with the degree of stabilization of the electrophilic intermediate. We found that these compounds are mutagenic (1-9 rev/nmole in Salmonella typhimurium TA98) and do not require S9 activation. However, this activity is substantially lower than that of other nitroPAH of comparable size such as 1-nitropyrene (250-300 rev/nmole). The reasons for this comparative lack of activity are discussed with reference to current theories regarding structure-activity relationships of nitroPAH.