COMPARATIVE MUTAGENICITY OF STRUCTURALLY RELATED ALIPHATIC EPOXIDES IN A MODIFIED SALMONELLA MICROSOME ASSAY

Four structurally related aliphatic epoxides (1,2-epoxypropane, 1,2-ep oxyisobutane, cis- and trans-2,3-epoxybutane) have been tested in the Salmonella/microsome assay, modified for volatile subtances, using the strains TA1535 and TA100. The aim of the study was to evaluate the ef fect of methylation on the mutagenicity of 1,2-epoxypropane in this va porization assay, with and without exogenous metabolization. All subst ances induced a significant increase of revertants in the strains TA15 35 and TA100. In terms of mutagenic potency, the following hierarchy w as observed in the standard tester strain TA1535 and in the absence of rat S9: 1,2-epoxypropane much greater than cis-2,3-epoxybutane > 1,2- epoxyisobutane > trans-2,3-epoxybutane. After exogenous metabolization , the mutagenic response of 1,2-epoxyisobutane was substantially reduc ed, while a moderate decrease of cis-2,3-epoxybutane was observed in t he presence of S9, as compared with the response without S9. No influe nce of the S9 on the mutagenic response of trans-2,3-epoxybutane was n oticed in both strains TA1535 and TA100, while an increased response w ith 1,2-epoxypropane was observed in TA100 but not in TA1535. The resu lts suggest that the vaporization assay may provide more relevant info rmation concerning mutagenic potencies of gaseous or volatile compound s than the common treat-and-plate or preincubation assays. Moreover, i t appears that mutagenicity theories, based only upon inductive effect s of side groups, may not suffice to explain differences in mutagenici ty. Sterical factors or differential interactions with metabolizing en zymes could also be important in the evaluation of mutagenic effects.