Biologically active aromatic amines derived from carcinogenic polycyclic aromatic hydrocarbons: synthesis and mutagenicity of aminobenzo[a]pyrenes.

The mutagenicities of 6-aminobenzo[a]pyrene (6-NH2-BP), 4-, 11- and 12-NH2-BP, and two N,N-diacetyl derivatives (4- and 12-N(Ac)2-BP) were compared to that of the present compound, BP, and to the aromatic amine, 2-aminofluorene (AF), in the Ames' Salmonella typhimurium assay. In the presence of an S9 activating system all the compounds were mutagenic in strains TA100, TA98 and TA1538 was 4-NH2-BP greater than 4-N(Ac)2-BP greater than 12-NH2-BP greater than 12-N(Ac)2-BP greater than AF greater than 11-NH2-BP congruent to BP greater than 6-NH2-BP; whereas in strain TA100, the order was 4-NH2-BP greater than 4-N(Ac)2-BP greater than BP greater than 12-NH2-BP congruent to 12-N(Ac)2-BP congruent to 11-NH2-BP greater than 6-NH2-BP congruent to AF. Inclusion of the deacylase inhibitor, paraoxon, in the incubation decreased the mutagenicity of 4-N(Ac)2-BP but had no effect on its primary amine. These data suggest that, at least for this group of compounds, arylamines derived from carcinogenic polycyclic aromatic hydrocarbons are activated to potent mutagens primarily through S9-mediated metabolism (e.g., N-oxidation) of the amine.