2006 Volume 7 Issue 1 Pages 22-29
3-Nitrobenzanthrone (3-NBA), present in air-born particulates and/or diesel exhaust particles, exhibits very strong mutagenicity. The mutagenic activities of its isomers, however, markedly decrease in the order 3- > 9- > 1-> 2- > 11-NBA and contrary to the usual way the activities of three dinitrobenzanthrones (DNBAs), 3,9-,1,9-, and 3,11-DNBA, arranged in the order of decreasing mutagenicity, are lower than that of the mononitrobenzanthrone, 3-NBA. To elucidate such specific behavior of NBAs and DNBAs in their mutagenicity theoretically, we postulated their metabolic activation pathway and calculated physicochemical properties, such as heats of formation, highest-occupied-molecular-orbital (HOMO) and lowest-unoccupied-molecular-orbital (LUMO) energies, of the parent molecules, metabolites, and ultimate mutagens by the semi-empirical molecular orbital method. The calculated results indicated that the difference in the mutagenicity of the isomeric NBAs and DNBAs originates from the LUMO energy of the parent molecules and nitrosometabolites; the lower their LUMO energy, the faster the rate of initial reductive reactions leading to formation of hydroxylamines. The decrease in the mutagenicity of the DNBAs is ascribed to lower HOMO energies of their hydroxylamino and amino metabolites compared with those of corresponding metabolites of the NBAs; the lower their HOMO energy, the faster their excretion.
