Studies on metabolism and toxicity of styrene: III. The effect of metabolic inactivation by rat-liver S9 on the mutagenicity of phenyloxirane toward Salmonella typhimurium.
A comparative study on enzymic factors influencing the metabolic inactivation of phenyloxirane (styrene oxide), a major mutagenic metabolite of styrene in the liver, was carried out with respect to soluble glutathione S-transferase and microsomal epoxide hydratase in the 9000 X g supernatant fraction (S9) from a rat-liver homogenate. The mutagenic activity of phenyloxirane to Salmonella typhimurium TA100 was markedly reduced by S9 in the presence of glutathione but to a smaller extent in its absence. The retarding effect of glutathione on the inherent mutagenic activity of phenyloxirane was exerted by the soluble supernatant of S9 but not by microsomes. A gas-liquid chromatographic study indicated that the effect of glutathione was attributable to the disappearance of the mutagen from the microbial assay system. The rate of the disappearance was 10-20 times as fast in the soluble supernatant fraction as in the microsomes when fortified with more than 4 mM glutathione. Our results strongly suggest that in hepatic cells of the rat, cytosol glutathione S-transferase plays a much more important role than microsomal epoxide hydratase in the detoxication of the metabolite, phenyloxirane.
D000818:Animals; D004851:Epoxide Hydrolases / Q000378:metabolism; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; 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; C013690:styrene oxide; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases