Journal Article

SHORT COMMUNICATION: Human glutathione S-transferase T1–1 enhances mutagenicity of 1, 2-dibromoethane, dibromomethane and 1,2,3,4-diepoxybutane in <i>Salmonella typhimurium</i>

Ricarda Thier, Sally E. Pemble, Harry Kramer, John B. Taylor, F.Peter Guengerich and Brian Ketterer

in Carcinogenesis

Volume 17, issue 1, pages 163-166
Published in print January 1996 | ISSN: 0143-3334
e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.1.163
SHORT COMMUNICATION: Human glutathione S-transferase T1–1 enhances mutagenicity of 1, 2-dibromoethane, dibromomethane and 1,2,3,4-diepoxybutane in Salmonella typhimurium

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The rat theta class glutathione S-transferase (GST) 5–5 has been shown to affect the mutagenicity of halogenated alkanes and epoxides. In Salmonella typhimurium TA1535 expressing the rat GST5–5 the number of revertants was increased compared to the control strain by CH2Br2, ethylene dibromide (EDB) and 1,2,3,4-diepoxybutane (BDE); in contrast, mutagenicity of 1,2-epoxy-3-(4'-nitro-phenoxy)propane (EPNP) was reduced. S.typhimurium TA1535 cells were transformed with an expression plasmid carrying the cDNA of the human theta ortholog GST1–1 either in sense or antisense orientation, the latter being the control. These transformed bacteria were utilized for mutagenicity assays. Mutagenicity of EDB, BDE, CH2Br2, epibromohydrin and 1,3-dichloroacetone was higher in the S.typhimurium TA1535 expressing GSTT1–1 than in the control strain. The expression of active enzyme did not affect the mutagenicity of 1, 2-epoxy-3-butene or propylene oxide. GSTT1–1 expression reduced the mutagenicity of EPNP. Glutathione S-transferase 5–5 and GSTT1–1 modulate genotoxicity of several industrially important chemicals in the same way. Polymorphism of the GSTT1 locus in humans may therefore cause differences in cancer susceptibility between the two phenotypes.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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