Inhibitory Effect of Dimethyl Sulfoxide on the Mutagenicity of Promutagens in the Ames Test

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The effect of dimethyl sulfoxide (DMSO) on the mutagenicity of 14 promutagens belonging to several chemical classes and one direct mutagen as a reference compound was examined in the Ames preincubation test, to clarify how much the test results were affected by its inhibitory activity on metabolic enzymes. The mutagens were assayed by the preincubation method using the TA100 or WP2uvrA(pKM101) bacterial test strains in the presence of 1% and 14% DMSO (concentrations in treatment mixture) with S9 mix for 12 promutagens that are known to be activated by CYP enzymes or without S9 mix for 2 promutagens that are known to be activated by bacterial nitroreductase enzymes, and the direct-mutagen. The data indicate that the mutagenicity of 11 of the 14 promutagens was significantly reduced in the presence of 14% DMSO as compared with that in the presence of 1% DMSO, while the 3 remaining promutagens and the direct mutagen exhibited mutagenicity of equal degree at both concentrations. The largest inhibitory effect of DMSO was found on the nitrosamines in WP2uvrA(pKM101) and TA100, and no cytotoxicity was detected by survival test, with 14% DMSO in WP2uvrA(pKM101), at any amounts of dimethylnitrosamine. Further equivalent or slightly lower cytotoxicity in the presence of 14% DMSO than in the presence of 1% DMSO was detected by decrease in the bacterial background-lawn density, as a whole. These observations suggest that the reduction in the yield of revertant colonies in the presence of 14% DMSO with the 11 chemicals was not due to cytotoxicity of DMSO. The inhibitory effect of DMSO on the mutagenicity of the promutagens can be explained by its inhibitory effect on the drug-metabolizing enzymes involved in the activation/detoxification pathways. Use of DMSO at a low concentration, such as 1%, may be suggested for the Ames test, as for other in vitro genotoxicity tests.<br>

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