| Name | glutathione S transferase |
|---|---|
| Synonyms | GST class alpha 2; Gst2; GST class alpha; GST class alpha member 2; GST gamma; GSTA 2; GSTA2; GSTA2 2… |
| Name | methylene chloride |
|---|---|
| CAS | dichloromethane |
| PubMed | Abstract | RScore(About this table) | |
|---|---|---|---|
| 8875160 | Thomas RS, Yang RS, Morgan DG, Moorman MP, Kermani HR, Sloane RA, O'Connor RW, Adkins B Jr, Gargas ML, Andersen ME: PBPK modeling/Monte Carlo simulation of methylene chloride kinetic changes in mice in relation to age and acute, subchronic, and chronic inhalation exposure. Environ Health Perspect. 1996 Aug;104(8):858-65. Using physiologically based pharmacokinetic (PBPK) modeling coupled with Monte Carlo simulation and bootstrap resampling for data analyses, a significant induction in the mixed function oxidase (MFO) rate constant (Vmaxc) was observed at the 1-day and 1-month exposure points when compared to concurrent control mice while decreases in glutathione S-transferase (GST) rate constant (Kfc) were observed in the 1-day and 1-month exposed mice. |
1(0,0,0,1) | Details |
| 1820733 | Reitz RH: Estimating the risk of human cancer associated with exposure to methylene chloride. Ann Ist Super Sanita. 1991;27(4):609-14. CH2Cl2 is extensively metabolized in mammalian species through two competing pathways: (1) oxidation by the mixed function oxidase enzymes, and (2) conjugation with catalyzed by glutathione-S-transferase (s)(GST). |
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| 1361146 | Manno M, Rugge M, Cocheo V: Double fatal inhalation of dichloromethane. Hum Exp Toxicol. 1992 Nov;11(6):540-5. However, biotransformation of the solvent to toxic metabolites, including (via oxidative dehalogenation by the cytochrome P450-dependent mixed function oxidase system) or inorganic and (via the glutathione-S-transferase pathway) may have also contributed significantly to fatal toxicity. |
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| 7979958 | Hallier E, Schroder KR, Asmuth K, Dommermuth A, Aust B, Goergens HW: Metabolism of dichloromethane (methylene chloride) to in human erythrocytes: influence of polymorphism of glutathione transferase theta (GST T1-1). Arch Toxicol. 1994;68(7):423-7. The formation of from dichloromethane is influenced by the polymorphism of glutathione-S-transferase (GST) Theta, in the same way as the metabolism of methyl methyl methyl iodide and ethylene oxide. |
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| 11453994 | Gisi D, Maillard J, Flanagan JU, Rossjohn J, Chelvanayagam G, Board PG, Parker MW, Leisinger T, Vuilleumier S: Dichloromethane mediated in vivo selection and functional characterization of rat glutathione S-transferase theta 1-1 variants. Eur J Biochem. 2001 Jul;268(14):4001-10. Methylobacterium dichloromethanicum DM4 is able to grow with dichloromethane as the sole carbon and energy source by using a dichloromethane dehalogenase/glutathione S-transferase (GST) for the conversion of dichloromethane to |
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| 8565906 | Leisinger T, Braus-Stromeyer SA: Bacterial growth with chlorinated methanes. Environ Health Perspect. 1995 Jun;103 Suppl 5:33-6. Sequence comparisons have shown that bacterial dichloromethane dehalogenases belong to the glutathione S-transferase enzyme family, and within this family to class Theta. |
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| 1375920 | Foster JR, Green T, Smith LL, Lewis RW, Hext PM, Wyatt I: Methylene chloride--an inhalation study to investigate pathological and biochemical events occurring in the lungs of mice over an exposure period of 90 days. Fundam Appl Toxicol. 1992 Apr;18(3):376-88. The glutathione S-transferase metabolism of MC by the lung cytosol remained virtually unaltered throughout the study. |
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| 8512599 | Bogaards JJ, van Ommen B, van Bladeren PJ: Interindividual differences in the in vitro conjugation of methylene chloride with by cytosolic glutathione S-transferase in 22 human liver samples. Biochem Pharmacol. 1993 May 25;45(10):2166-9. |
162(2,2,2,2) | Details |
| 8670055 | Mainwaring GW, Nash J, Davidson M, Green T: Isolation of a mouse theta glutathione S-transferase active with methylene chloride. Biochem J. 1996 Mar 1;314 ( Pt 2):445-8. A glutathione S-transferase metabolizing methylene chloride has been isolated from mouse liver using a variety of chromatographic methods. |
87(1,1,2,2) | Details |
| 8761485 | Mainwaring GW, Williams SM, Foster JR, Tugwood J, Green T: The distribution of theta-class glutathione S-transferases in the liver and lung of mouse, rat and human. Biochem J. 1996 Aug 15;318 ( Pt 1):297-303. The relative activities between species, and the cellular and sub-cellular distribution within the liver and lungs of each species, provides an explanation for the species-specificity of methylene chloride, a mouse-specific carcinogen activated by glutathione S-transferase GSTT1-1. |
83(1,1,1,3) | Details |
| 9506258 | Liteplo RG, Long GW, Meek ME: Relevance of carcinogenicity bioassays in mice in assessing potential health risks associated with exposure to methylene chloride. Hum Exp Toxicol. 1998 Feb;17(2):84-7. On the basis of a study that purported to show qualitative differences between murine and human tissues, in the subcellular localization of the Theta-class glutathione S-transferase enzyme responsible for converting methylene chloride to a putative highly unstable, but reactive genotoxic metabolite, it was suggested that the mouse is an inappropriate model for human health risk assessment. |
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| 8600370 | Graves RJ, Green T: Mouse liver glutathione S-transferase mediated metabolism of methylene chloride to a mutagen in the CHO/HPRT assay. Mutat Res. 1996 Mar 1;367(3):143-50. |
82(1,1,1,2) | Details |
| 8671744 | Graves RJ, Trueman P, Jones S, Green T: DNA sequence analysis of methylene chloride-induced HPRT mutations in Chinese hamster ovary cells: comparison with the mutation spectrum obtained for 1,2-dibromoethane and Mutagenesis. 1996 May;11(3):229-33. Glutathione-S-transferase-mediated metabolism of methylene chloride (MC) generates S-chloromethylglutathione, which has the potential to react with DNA, and which is a known mutagen. |
81(1,1,1,1) | Details |
| 8998946 | Casanova M, Conolly RB, Heck H d'A: DNA-protein cross-links (DPX) and cell proliferation in B6C3F1 mice but not Syrian golden hamsters exposed to dichloromethane: pharmacokinetics and risk assessment with DPX as dosimeter. Fundam Appl Toxicol. 1996 May;31(1):103-16. Dichloromethane (DCM) (methylene chloride; CH2Cl2) is metabolized via a glutathione S-transferase-mediated pathway to (HCHO), a mutagenic compound that could play a role in the carcinogenic effects of DCM observed in the liver and lungs of B6C3F1 mice at 2000 and 4000 ppm. |
81(1,1,1,1) | Details |
| 7482565 | Rhomberg L: Use of quantitative modelling in methylene chloride risk assessment. Toxicology. 1995 Sep 1;102(1-2):95-114. The internal dose measure was the daily amount of methylene chloride metabolized by a glutathione-S-transferase pathway per 1 of target organ (liver and lung). |
31(0,1,1,1) | Details |
| 7702765 | Yin XJ, Liu JZ, Li YS, Kong XH, Liu H: Mutagenicity and induction of drug-metabolizing enzyme activity by LPG combustion particulates in rats. Biomed Environ Sci. 1994 Dec;7(4):346-56. Methylene chloride extracts of particulates from liquefied petroleum gas (LPG) combustion appliance were studied by using Ames test, micronucleus test and inducibility of pulmonary and hepatic aryl hydrocarbon hydroxylase (AHH) and glutathione S-transferase (GST) in rats. |
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| 10350186 | Gisi D, Leisinger T, Vuilleumier S: Enzyme-mediated dichloromethane toxicity and mutagenicity of bacterial and mammalian dichloromethane-active glutathione S-transferases. Arch Toxicol. 1999 Mar;73(2):71-9. |
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| 8132617 | Blocki FA, Logan MS, Baoli C, Wackett LP: Reaction of rat liver glutathione S-transferases and bacterial dichloromethane dehalogenase with dihalomethanes. J Biol Chem. 1994 Mar 25;269(12):8826-30. |
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| 8494496 | Hallier E, Langhof T, Dannappel D, Leutbecher M, Schroder K, Goergens HW, Muller A, Bolt HM: Polymorphism of conjugation of methyl ethylene oxide and dichloromethane in human blood: influence on the induction of sister chromatid exchanges (SCE) in lymphocytes. Arch Toxicol. 1993;67(3):173-8. A hitherto unknown glutathione-S-transferase in human erythrocytes displays polymorphism: three quarters of the population ("conjugators") possess, whereas one quarter ("non-conjugators") lack this specific activity. Three substrates of the polymorphic enzyme, methyl ethylene oxide and dichloromethane (methylene chloride), were incubated in vitro with individual whole blood samples of conjugators and non-conjugators. |
2(0,0,0,2) | Details |
| 10876998 | Schulz TG, Wiebel FA, Thier R, Neubert D, Davies DS, Edwards RJ: Identification of theta-class glutathione S-transferase in liver cytosol of the marmoset monkey. Arch Toxicol. 2000 May;74(3):133-8. |
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| 8330352 | Simula TP, Glancey MJ, Wolf CR: Human glutathione S-transferase-expressing Salmonella typhimurium tester strains to study the activation/detoxification of mutagenic compounds: studies with halogenated compounds, aromatic amines and Carcinogenesis. 1993 Jul;14(7):1371-6. |
2(0,0,0,2) | Details |
| 7765835 | Leisinger T, Bader R, Hermann R, Schmid-Appert M, Vuilleumier S: Microbes, enzymes and genes involved in dichloromethane utilization. Biodegradation. 1994 Dec;5(3-4):237-48. DCM dehalogenase belongs to the glutathione S-transferase supergene family. |
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| 11238968 | Vuilleumier S, Ivos N, Dean M, Leisinger T: Sequence variation in dichloromethane dehalogenases/glutathione S-transferases. Microbiology. 2001 Mar;147(Pt 3):611-9. |
2(0,0,0,2) | Details |
| 9435885 | DeMarini DM, Shelton ML, Warren SH, Ross TM, Shim JY, Richard AM, Pegram RA: Glutathione S-transferase-mediated induction of GC--> AT transitions by halomethanes in Salmonella. Environ Mol Mutagen. 1997;30(4):440-7. |
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| 8206823 | Bader R, Leisinger T: Isolation and characterization of the Methylophilus sp. strain DM11 gene encoding dichloromethane dehalogenase/glutathione S-transferase. J Bacteriol. 1994 Jun;176(12):3466-73. |
2(0,0,0,2) | Details |
| 11489877 | Kayser MF, Vuilleumier S: Dehalogenation of dichloromethane by dichloromethane dehalogenase/glutathione S-transferase leads to formation of DNA adducts. J Bacteriol. 2001 Sep;183(17):5209-12. |
2(0,0,0,2) | Details |
| 8079362 | Foster JR, Green T, Smith LL, Tittensor S, Wyatt I: Methylene chloride: an inhalation study to investigate toxicity in the mouse lung using morphological, biochemical and Clara cell culture techniques. Toxicology. 1994 Aug 12;91(3):221-34. Both cytochrome P-450 (CYP)- and glutathione S-transferase (GST)-dependent metabolism of MC are known to occur. |
1(0,0,0,1) | Details |
| 8806840 | Kim C, Manning RO, Brown RP, Bruckner JV: Use of the vial equilibration technique for determination of metabolic rate constants for dichloromethane. Toxicol Appl Pharmacol. 1996 Aug;139(2):243-51. Metabolism of methylene chloride, or dichloromethane (DCM), plays a key role in determining the kinetics and carcinogenicity of the halocarbon. The objectives of this study were: to evaluate and optimize the vial equilibration technique, originally described by Sato and Nakajima (1979a), in order to characterize the hepatic metabolism of DCM by Sprague-Dawley rats; to employ different hepatic microsomal preparations to examine buffer effects on DCM metabolism; and to assess the relative importance and metabolic constants of the mixed-function oxidase (MFO) and glutathione (GSH) S-transferase (GST) metabolic pathways. |
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| 9242590 | Casanova M, Bell DA, Heck HD: Dichloromethane metabolism to and reaction of with nucleic acids in hepatocytes of rodents and humans with and without glutathione S-transferase T1 and M1 genes. Fundam Appl Toxicol. 1997 Jun;37(2):168-80. Metabolism of dichloromethane (DCM) to (HCHO) via a glutathione S-transferase (GST) pathway is thought to be required for its carcinogenic effects in B6C3F1 mice. |
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| 11065375 | Evans GJ, Ferguson GP, Booth IR, Vuilleumier S: Growth inhibition of Escherichia coli by dichloromethane in cells expressing dichloromethane dehalogenase/glutathione S-transferase. Microbiology. 2000 Nov;146 ( Pt 11):2967-75. |
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| 9792420 | Quondamatteo F, Schulz TG, Bunzel N, Hallier E, Herken R: Immunohistochemical localization of glutathione S-transferase-T1 in murine kidney, liver, and lung. Histochem Cell Biol. 1998 Oct;110(4):417-23. Glutathione S-transferase-mediated metabolism of exogenous compounds usually leads to detoxification, but there are some exceptions. |
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| 8055623 | Himmelstein MW, Turner MJ, Asgharian B, Bond JA: Comparison of blood concentrations of 1,3-butadiene and butadiene epoxides in mice and rats exposed to 1,3-butadiene by inhalation. Carcinogenesis. 1994 Aug;15(8):1479-86. BD epoxides were extracted into methylene chloride and quantified by gas chromatography-mass spectrometry. Detoxication of the epoxides occurs by glutathione S-transferase-catalyzed conjugation with and hydrolysis by epoxide hydrolase. |
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| 9023569 | Green T: Methylene chloride induced mouse liver and lung tumours: an overview of the role of mechanistic studies in human safety assessment. Hum Exp Toxicol. 1997 Jan;16(1):3-13. The species specificity was a direct consequence of the very high activity and specific cellular and nuclear localisation of a theta class glutathione S-transferase enzyme which was unique to the mouse. |
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| 8035742 | Soleo L: [The detoxification pathways of electrophilic intermediate compounds] . Med Lav. 1994 Jan-Feb;85(1):22-36. Also in the case of methylene chloride, the greater susceptibility of the mouse to develop tumours compared with the rat seems to be connected with a greater production of S-chloromethyl-GSH in the mouse, although no specific oncogenic action has yet been demonstrated for this reactive intermediate. Another route consists of conjugation of intermediate electrophiles with via a glutathione-S-transferase or spontaneously. |
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| 2922756 | Reitz RH, Mendrala AL, Guengerich FP: In vitro metabolism of methylene chloride in human and animal tissues: use in physiologically based pharmacokinetic models. Toxicol Appl Pharmacol. 1989 Feb;97(2):230-46. However, one limitation of this PB-PK model was that the metabolic rate constants for the glutathione-S-transferase (GST) pathway in humans were estimated by allometric scaling rather than from experimental data. |
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| 16765633 | Hu Y, Kabler SL, Tennant AH, Townsend AJ, Kligerman AD: Induction of DNA-protein crosslinks by dichloromethane in a V79 cell line transfected with the murine glutathione-S-transferase theta 1 gene. Mutat Res. 2006 Sep 5;607(2):231-9. Epub 2006 Jun 12. Despite the correlation between metabolism of DCM by the glutathione-S-transferase (GST) pathway and the occurrence of tumors in different species, the mechanism of tumor induction by DCM metabolites produced through the GST pathway remains unclear. |
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| 14727918 | Marsch GA, Botta S, Martin MV, McCormick WA, Guengerich FP: Formation and mass spectrometric analysis of DNA and nucleoside adducts by S-(1-acetoxymethyl) and by glutathione S-transferase-mediated activation of dihalomethanes. Chem Res Toxicol. 2004 Jan;17(1):45-54. |
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| 10986246 | Kayser MF, Stumpp MT, Vuilleumier S: DNA polymerase I is essential for growth of Methylobacterium dichloromethanicum DM4 with dichloromethane. J Bacteriol. 2000 Oct;182(19):5433-9. Methylobacterium dichloromethanicum DM4 grows with dichloromethane as the unique carbon and energy source by virtue of a single enzyme, dichloromethane dehalogenase-glutathione S-transferase. |
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