Analysis of mutagenicity of nitrobenzanthrones by molecular orbital calculations

3-Nitrobenzanthrone (3-NBA) detected in diesel exhaust was found to be a very strong mutagen. 9-NBA, however, is less potent than 3-NBA and 11-NBA is devoid of mutagenicity. To explain the difference in mutagenicity among the three isomers theoretically, we proposed the metabolic activation pathway of NBAs and performed molecular orbital calculations. In the pathway, NBAs are transformed to nitrosobenzanthrone, N-hydroxy-3-aminobenzanthrone (N-OH-ABA), N-acetoxy-3-aminobenzanthrone (N-AcO-ABA), and finally ultimate carcinogens to form NBA-DNA adducts. We calculated the heat of formation, HOMO and LUMO energy for parent molecules and their activated intermediates. The activation energy (Ea) was also calculated for the binding reaction of the ultimate carcinogens with the DNA bases. A correlation was found between the mutagenicity of NBAs and the LUMO energy of parent molecules and the intermediates, nitrosobenzanthrone, N-OH-ABA, and N-AcO-ABA. The Ea values were not correlated with mutagenicity. This indicates that the production rate and stability of ultimate carcinogens are more important in determining the mutagenicity than the reaction rate of their binding to DNA.