Enhancement of Bacterial Mutagenicity of Bifunctional Alkylating Agents by Expression of Mammalian Glutathione S-Transferase
| Autor: | J B Taylor, S E Pemble, Brian Ketterer, Müller M, F. P. Guengerich, Ricarda Thier |
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| Rok vydání: | 1995 |
| Předmět: |
Salmonella typhimurium
Alkylating Agents Insecticides Glutathione reductase Mutant Toxicology Propane chemistry.chemical_compound Complementary DNA Animals Mutagen testing Glutathione Transferase biology Mutagenicity Tests Chemistry Drug Synergism General Medicine Transfection Glutathione biology.organism_classification Molecular biology Rats Glutathione S-transferase Biochemistry biology.protein Bacteria Mutagens |
| Zdroj: | Chemical Research in Toxicology. 8:465-472 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/tx00045a019 |
| Popis: | Recently, we inserted the plasmid vector pKK233-2 containing rat GSH S-transferase (GST) 5-5 cDNA into Salmonella typhimurium TA1535 and found that these bacteria [GST 5-5(+)] expressed the protein and produced mutations when ethylene or methylene dihalides were added [Thier, R., Taylor, J. B., Pemble, S. E., Ketterer, B., Persmark, M., Humphreys, W. G., and Guengerich, F. P. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 8576-8580]. After exposure to the known GST 5-5 substrate 1,2-epoxy-3-(4'-nitrophenoxy)propane, the GST 5-5(+) strain showed fewer mutants than the bacteria transfected with the cDNA clone in a reverse orientation [GST 5-5(-)], suggesting a protective role of GST 5-5. However, mutations were considerably enhanced in the GST 5-5(+) strain [as compared to GST 5-5(-)] when 1,2,3,4-diepoxybutane (butadiene diepoxide) or 1,2-epoxy-4-bromobutane was added. The GST 5-5(+) and GST 5-5(-) bacterial stains showed similar responses to 1,2-epoxypropane, 3,4-epoxy-1-butene, and 1,4-dibromobutane. The results suggest that some bifunctional activated butanes are transformed to mutagenic products through GSH conjugation. We also found that the GST 5-5(+) strain showed enhanced mutagenicity with 1,4-dibromo-2,3-epoxybutane, 1,2-epoxy-3-bromopropane (epibromohydrin), and (+/-)-1,4-dibromo-2,3-dihydroxybutane.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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