The effect of hepatic microsomal and cytosolic subcellular fractions on the mutagenic activity of epoxide-containing compounds in the Salmonella assay.
7 epoxide-containing compounds: allylbenzene oxide, styrene oxide, trans-beta-methylstyrene oxide, 4-chlorophenyl glycidyl ether, vinylcyclohexene dioxide, octene dioxide and hexene dioxide were evaluated for mutagenic activity in 4 histidine-requiring strains of Salmonella typhimurium, namely: TA1535, TA100, TA1537 and TA98. These epoxides, except trans-beta-methylstyrene oxide, were mutagenic in TA1535 and TA100 but none of the tested compounds caused mutations in strains TA1537 and TA98. Both the cytosolic (100000 g soluble) and/or microsomal (100000 g pellet) fractions derived from noninduced mouse, guinea pig, and/or rat consistently decreased the mutagenic activity of the 3 most active mutagens: allylbenzene oxide, styrene oxide and 4-chlorophenyl glycidyl ether. This reduction was found to depend on the substrate and the source of the enzyme fraction. Glutathione alone or in combination with the mouse cytosolic fraction resulted in negligible suppression in the mutagenic activity of the 3 epoxides under the conditions reported in this paper. The enzyme(s) in the cytosol responsible for the reduction in mutagenicity co-eluted from gel filtration with the epoxide hydrolase activity. These data are not consistent with the assumption that all epoxide hydrolase activity in an "S9" fraction is microsomal.
D000818:Animals; D001711:Biotransformation; D003600:Cytosol / Q000201:enzymology; D004851:Epoxide Hydrolases / Q000378:metabolism; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006168:Guinea Pigs; D008099:Liver / Q000201:enzymology; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D009152:Mutagenicity Tests; D009153:Mutagens; D051381:Rats; D012486:Salmonella typhimurium / Q000235:genetics
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D009153:Mutagens; D004851:Epoxide Hydrolases