Bacterial mutagenicity and toxicity of cycloaliphatic epoxides

The mutagenicity of 12 cycloaliphatic epoxides was investigated using the Ames Salmonella assay without the addition of liver homogenate fractions. Base-pair substitution mutagenic activity was detected for 8 members of this series of compounds, confirming our laboratory's previous observations of weak mutagenic response at high dose levels for cis-1,2-disubstituted epoxides. While mutagenicity decreased with expanding ring size, inhibition of bacterial growth increased for increases in ring size. Toxicity accompanying the required high doses for the demonstration of mutagenicity for these compounds prevented the establishment of meaningful dose-response ranges for the remaining epoxides tested. The volatility observed with these oxiranes also made dose-response establishment difficult but was countered by the use of petri dish sealing bands during incubation. Mutagenicity in this series was found to be generally more pronounced in TA1535 while toxicity was detected with greater sensitivity by TA100. The use of the less permeable strains TA92, TA1950 and TA2410, all having normal lipopolysaccharide cell wall coatings, failed to reduce this marked toxicity. The repair test compared results in TA1535 (repair-deficient strain) with TA1975 (repair-proficient strain) and demonstrated that the bacteria were not being killed by damage to DNA since toxicity was not reduced in TA1975.