Mutagenicity of nitrodibenzopyranones in the Salmonella plate-incorporation and microsuspension assays

Abstract

The mutagenicity of three isomers of nitro-6 H-dibenzo[ b, d]pyran-6-one (NDBP), 2-NDBP, 3-NDBP and 4-NDBP, was characterized in the plate-incorporation (PI) and microsuspension (MS) assay using Salmonella typhimurium tester strains in the presence or absence of S9 mix. In both assays, all of the NDBPs showed mutagenicity in every strain. In the absence of S9 mix, TA98 was the strain most sensitive to the mutagenicity of NDBPs. The activity of NDBPs was reduced in TA98NR and TA98/1,8-DNP 6 strains relative to TA98, suggesting that NDBPs cause frameshift mutation and that nitroreduction by ‘classical’ nitroreductase and acetylation are significant steps for their metabolic activation. Mutagenic potency of NDBPs in TA98 without S9 mix in the MS assay (2-NDBP 104 300 rev./μg, 3-NDBP 23 500 rev./μg, and 4-NDBP 15 300 rev./μg) was much higher than that in the PI assay (2-NDBP 38 rev./μg, 3-NDBP 162 rev./μg, and 4-NDBP 7 rev./μg). Although additional S9 mix increased the mutagenicity of NDBPs in the PI assay, the mutagenic potency of NDBPs in the MS assay using strains TA98 and TA100 was decreased by the addition of S9 mix. In the PI assay, frameshift and base-substitution activities of both isomers were enhanced by the addition of the pKM101 plasmid, suggesting the induction by these isomers of complex frameshifts (frameshifts with associated base substitutions) in strain TA98. In the PI assay, 2-NDBP generally exhibited more base-substitution than frameshift activity; however, the reverse was true for 3-NDBP. In the MS assay, both isomers exhibited more frameshift than base-substitution activity.