Comparative mutagenicity of structurally related aliphatic epoxides in a modified Salmonella/microsome assay.

P Castelain, B Criado, M Cornet, R Laib, V Rogiers, M Kirsch-Volders

Index: Mutagenesis 8(5) , 387-93, (1993)

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Abstract

Four structurally related aliphatic epoxides (1,2-epoxypropane, 1,2-epoxyisobutane, cis- and trans-2,3-epoxybutane) have been tested in the Salmonella/microsome assay, modified for volatile substances, using the strains TA1535 and TA100. The aim of the study was to evaluate the effect of methylation on the mutagenicity of 1,2-epoxypropane in this vaporization assay, with and without exogenous metabolization. All substances induced a significant increase of revertants in the strains TA1535 and TA100. In terms of mutagenic potency, the following hierarchy was observed in the standard tester strain TA1535 and in the absence of rat S9: 1,2-epoxy-propane >> cis-2,3-epoxybutane > 1,2-epoxyisobutane > trans-2,3- epoxybutane. After exogenous metabolization, the mutagenic response of 1,2-epoxyisobutane was substantially reduced, while a moderate decrease of cis-2,3-epoxybutane was observed in the presence of S9, as compared with the response without S9. No influence of the S9 on the mutagenic response of trans-2,3-epoxybutane was noticed in both strains TA1535 and TA100, while an increased response with 1,2-epoxypropane was observed in TA100 but not in TA1535. The results suggest that the vaporization assay may provide more relevant information concerning mutagenic potencies of gaseous or volatile compounds than the common treat-and-plate or preincubation assays. Moreover, it appears that mutagenicity theories, based only upon inductive effects of side groups, may not suffice to explain differences in mutagenicity. Sterical factors or differential interactions with metabolizing enzymes could also be important in the evaluation of mutagenic effects.