Micronucleus induction and chromosomal aberration of 1-and 3-nitroazabenzo[a]pyrene and their N-oxides

Nitro-azabenzo[a]pyrenes, 1- or 3-nitro-azabenzo[a]pyrene and their N-oxide s are nitrated derivatives of azabenzo[a] pyrene (ABP) containing nitrogen in the 6-position of benzo[a]pyrene (B[a]P), The nitro-ABP-N-oxides (ABPOs) were formed by reaction of ABP with excess HNO3. These derivatives were no teworthy as potent mutagens for Salmonella strains, and were present in fin e particles of diesel particulates. In this study, micronucleus induction i n mice and chromosomal aberrations due to means of Chinese hamster lung fib roblast (CHL) cells were investigated to determine genotoxicity in order to define the relationship with the mutagenic potency of these derivatives. T he induction of micronucleus polychromatic erythrocytes (MNPCEs) was depend ent on the dose response of 10-40 mg for 3-N-6-ABP, and of 10-40 mg for 1-N -6-ABP, and in addition, 1- and 3-N-6-ABPOs markedly induced MNPCEs in a do se range of 10-400 mg and from 1 to 80 mg, respectively, when the compound was intraperitoneally administrated in two mice at each dose. The results s how that of the four compounds, 3-N-6-ABPO demonstrated a marked increase i n MNPCEs, On the other hand, chromosomal aberrations of the four compounds were investigated by the duplicate tests using CHLs. The results after a 48 h treatment induced aberrations of the chromatid type, chromatid breaks an d exchanges for 1-and 3-N-6-ABP, and mainly chromatid exchanges for 1- and 3-N-6-ABPO. The frequency of chromosomal aberrations associated with nitro substitution on the ABPO structure. Chromosomal aberrations of nitro deriva tives of ABPO substituted at the 3-position on the structure were more pote nt than those at the 1-postion, N-oxide derivatives have been found to be r educed to anion radicals much more easily than azaB[a]P and its nitro deriv atives. This suggests that the electrochemical reduction of the chemicals p lays an important role in the metabolic activation of nitrated B[a]P deriva tives.