Glutathione and glutathione S-transferases in the Salmonella mammalian-microsome mutagenicity test.
Levels of the tripeptide glutathione (GSH) and the activity of glutathione S-transferases were investigated in S9 fractions of rats and mice and in Salmonella typhymurium tester strains TA1535, TA100, TA1538 and TA98. The S9 and Salmonella typhimurium tester strains had high levels of glutathione. Compared with S9, the activity of GSH S-transferases was lower in the bacteria. However, electrophiles such as 1-chloro-2,4-dinitrobenzene (CDNB), diethyl maleate and styrene oxide were effectively bound to bacterial GSH. The mutagenicity of the direct mutagen CDNB was drastically lowered in presence of S9 fractions but not in presence of microsomes. A comparable decrease was obtained when microsomal supernatant, which contains GSH and GSH S-transferases, was added to the microsomes. Addition of GSH in excess completely abolished mutagenicity of CDNB. These results demonstrate that the conjugation of electrophiles with GSH mediated by the S9 fraction or the bacterial tester strains represents an important detoxication mechanism which may influence the results obtained with the Salmonella typhimurium mammalian-microsome mutagenicity test.
D000818:Animals; D004136:Dinitrobenzenes / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D008298:Maleates / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism; D051381:Rats; D012486:Salmonella typhimurium / Q000201:enzymology / Q000378:metabolism*; D013343:Styrenes / Q000378:metabolism
D004136:Dinitrobenzenes; D008298:Maleates; D009153:Mutagens; D013343:Styrenes; D005982:Glutathione Transferase; D005978:Glutathione