Effects of the nitro-group on the mutagenicity and toxicity of some benzamines

The Ames Salmonella/microsomal assay was employed to test the mutagenicity of some benzamines (aniline, and o‐ and p‐phenylenediamine) and their nitro‐derivatives (p‐nitroaniline, 2‐nitro‐p‐phenylenediamine 3‐ and 4‐nitro‐o‐phenylenediamine), using strains TA98) and TA100 and their nitroreductase‐deficient mutants, TA98NR and TA100NR, in the presence and absence of rat S9 mix. The addition of the nitro‐group to benzamine molecules converted them into direct mutagens. Furthermore, the position of the nitro‐group affected their mutagenic activities. Cytotoxicity testing with Chinese hamster ovary cells (CHO‐K1) showed that the presence of the nitro‐group in these compounds had no specific effect on toxicity. The test compounds all showed a dose‐related increase in inducing chromosomal aberrations in CHO cells. However, the presence of the nitro‐group did not affect potency in inducing chromosomal aberrations. Compounds containing the nitro‐group had higher initial oxidation potentials and dipole moments (μ) than their nonnitro‐containing counterparts. The mutagenicity and toxicity of these compounds were not related to physico‐chemical properties, including oxidation potential, energy difference (ΔE) between the lowest unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital (HOMO), ionization potential (I.P.), and μ. © 1996 Wiley‐Liss, Inc.