Human glutathione S-transferase T1-1 enhances mutagenicity of 1,2-dibromoethane, dibromomethane and 1,2,3,4-diepoxybutane in Salmonella typhimurium

Thier, Ricarda, Pemble, Sally E., Kramer, Harry, Taylor, Jennifer, Guengerich, F. Peter, & Ketterer, Brian (1996) Human glutathione S-transferase T1-1 enhances mutagenicity of 1,2-dibromoethane, dibromomethane and 1,2,3,4-diepoxybutane in Salmonella typhimurium. Carcinogenesis, 17(1), pp. 163-166.

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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'-nitrophenoxy)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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ID Code: 77492
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Keywords: 1, 2 dibromoethane, alkane derivative, butadiene diepoxide, complementary dna, dibromomethane, epoxide, glutathione transferase, mutagenic agent, article, cell transformation, controlled study, enzyme activity, expression vector, mutagen testing, mutagenicity, nonhuman, plasmid, priority journal, revertant, salmonella typhimurium, Animals, Epoxy Compounds, Ethylene Dibromide, Humans, Hydrocarbons, Brominated, Mutagens, Rats
DOI: 10.1093/carcin/17.1.163
ISSN: 0143-3334
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 1996 Oxford University Press
Deposited On: 16 Oct 2014 02:14
Last Modified: 28 Jan 2015 02:25

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