Human glutathione S-transferase T1-1 enhances mutagenicity of 1,2-dibromoethane, dibromomethane and 1,2,3,4-diepoxybutane in Salmonella typhimurium.
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.
Thier
R
R
University College of London, Department of Biochemistry, UK.
Pemble
S E
SE
Kramer
H
H
Taylor
J B
JB
Guengerich
F P
FP
Ketterer
B
B
D000818:Animals; D004852:Epoxy Compounds / Q000633:toxicity*; D015946:Ethylene Dibromide / Q000633:toxicity; D005982:Glutathione Transferase / Q000633:toxicity*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics
D004852:Epoxy Compounds; D006842:Hydrocarbons, Brominated; D009153:Mutagens; D015946:Ethylene Dibromide; C007366:diepoxybutane; D005982:Glutathione Transferase; C027947:methylene bromide