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. 1996 Aug 15;318(Pt 1):297–303. doi: 10.1042/bj3180297

The distribution of theta-class glutathione S-transferases in the liver and lung of mouse, rat and human.

G W Mainwaring 1, S M Williams 1, J R Foster 1, J Tugwood 1, T Green 1
PMCID: PMC1217621  PMID: 8761485

Abstract

Two murine Theta-class glutathione S-transferases (GSTs), mGSTT1 and mGSTT2, have been cloned and sequenced. The murine cDNAs, together with the published sequences of the rat and human enzymes, were used to design oligonucleotide probes in order to determine the distribution of mRNA for these enzymes in the liver and lung of rat, mouse and human. The mRNA distribution was compared with that of enzyme protein determined with an antibody to rat GSTT2-2. Both the antibody and the oligonucleotide probes gave the same distribution patterns. Both enzymes were present at significantly higher concentrations in mouse tissues than in rat or human tissues. In mouse liver, both enzymes were localized in specific cell types and in nuclei. Although the distribution of GSTT2-2 in rat liver was similar to that seen in the mouse, GSTT1-1 was not localized in a specific cell type or in the nuclei of either rat or human liver. In the lungs, very high concentrations of the Theta enzymes were present in mouse-lung Clara cells and ciliated cells, with much lower levels in the Clara cells only of rat lung. Low levels of human transferase GSTT1-1 were detected in a small number of Clara cells and ciliated cells at the alveolar/ bronchiolar junction. 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.

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Selected References

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  1. Abei M., Harada S., Tanaka N., McNeil M., Osuga T. Immunohistochemical localization of human liver glutathione S-transferase (GST) isozymes with special reference to polymorphic GST1. Biochim Biophys Acta. 1989 May 1;995(3):279–284. doi: 10.1016/0167-4838(89)90047-2. [DOI] [PubMed] [Google Scholar]
  2. Ahmed A. E., Anders M. W. Metabolism of dihalomethanes to formaldehyde and inorganic halide. I. In vitro studies. Drug Metab Dispos. 1976 Jul-Aug;4(4):357–361. [PubMed] [Google Scholar]
  3. Bammler T. K., Smith C. A., Wolf C. R. Isolation and characterization of two mouse Pi-class glutathione S-transferase genes. Biochem J. 1994 Mar 1;298(Pt 2):385–390. doi: 10.1042/bj2980385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bennett C. F., Spector D. L., Yeoman L. C. Nonhistone protein BA is a glutathione S-transferase localized to interchromatinic regions of the cell nucleus. J Cell Biol. 1986 Feb;102(2):600–609. doi: 10.1083/jcb.102.2.600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  6. Burek J. D., Nitschke K. D., Bell T. J., Wackerle D. L., Childs R. C., Beyer J. E., Dittenber D. A., Rampy L. W., McKenna M. J. Methylene chloride: a two-year inhalation toxicity and oncogenicity study in rats and hamsters. Fundam Appl Toxicol. 1984 Feb;4(1):30–47. doi: 10.1016/0272-0590(84)90217-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  8. Graves R. J., Coutts C., Eyton-Jones H., Green T. Relationship between hepatic DNA damage and methylene chloride-induced hepatocarcinogenicity in B6C3F1 mice. Carcinogenesis. 1994 May;15(5):991–996. doi: 10.1093/carcin/15.5.991. [DOI] [PubMed] [Google Scholar]
  9. Graves R. J., Coutts C., Green T. Methylene chloride-induced DNA damage: an interspecies comparison. Carcinogenesis. 1995 Aug;16(8):1919–1926. doi: 10.1093/carcin/16.8.1919. [DOI] [PubMed] [Google Scholar]
  10. Guengerich F. P. Metabolic activation of carcinogens. Pharmacol Ther. 1992;54(1):17–61. doi: 10.1016/0163-7258(92)90050-a. [DOI] [PubMed] [Google Scholar]
  11. Hallier E., Langhof T., Dannappel D., Leutbecher M., Schröder K., Goergens H. W., Müller A., Bolt H. M. Polymorphism of glutathione conjugation of methyl bromide, ethylene oxide and dichloromethane in human blood: influence on the induction of sister chromatid exchanges (SCE) in lymphocytes. Arch Toxicol. 1993;67(3):173–178. doi: 10.1007/BF01973304. [DOI] [PubMed] [Google Scholar]
  12. Hallier E., Schröder K. R., Asmuth K., Dommermuth A., Aust B., Goergens H. W. Metabolism of dichloromethane (methylene chloride) to formaldehyde in human erythrocytes: influence of polymorphism of glutathione transferase theta (GST T1-1). Arch Toxicol. 1994;68(7):423–427. doi: 10.1007/s002040050092. [DOI] [PubMed] [Google Scholar]
  13. Harris J. M., Meyer D. J., Coles B., Ketterer B. A novel glutathione transferase (13-13) isolated from the matrix of rat liver mitochondria having structural similarity to class theta enzymes. Biochem J. 1991 Aug 15;278(Pt 1):137–141. doi: 10.1042/bj2780137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hayes J. D., Pulford D. J. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol. 1995;30(6):445–600. doi: 10.3109/10409239509083491. [DOI] [PubMed] [Google Scholar]
  15. Hussey A. J., Hayes J. D. Characterization of a human class-Theta glutathione S-transferase with activity towards 1-menaphthyl sulphate. Biochem J. 1992 Sep 15;286(Pt 3):929–935. doi: 10.1042/bj2860929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ketterer B. Detoxication reactions of glutathione and glutathione transferases. Xenobiotica. 1986 Oct-Nov;16(10-11):957–973. doi: 10.3109/00498258609038976. [DOI] [PubMed] [Google Scholar]
  17. La Roche S. D., Leisinger T. Sequence analysis and expression of the bacterial dichloromethane dehalogenase structural gene, a member of the glutathione S-transferase supergene family. J Bacteriol. 1990 Jan;172(1):164–171. doi: 10.1128/jb.172.1.164-171.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mainwaring G. W., 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):445–448. doi: 10.1042/bj3140445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mannervik B., Danielson U. H. Glutathione transferases--structure and catalytic activity. CRC Crit Rev Biochem. 1988;23(3):283–337. doi: 10.3109/10409238809088226. [DOI] [PubMed] [Google Scholar]
  20. Meyer D. J., Coles B., Pemble S. E., Gilmore K. S., Fraser G. M., Ketterer B. Theta, a new class of glutathione transferases purified from rat and man. Biochem J. 1991 Mar 1;274(Pt 2):409–414. doi: 10.1042/bj2740409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. NASH T. The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem J. 1953 Oct;55(3):416–421. doi: 10.1042/bj0550416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ogura K., Nishiyama T., Okada T., Kajital J., Narihata H., Watabe T., Hiratsuka A., Watabe T. Molecular cloning and amino acid sequencing of rat liver class theta glutathione S-transferase Yrs-Yrs inactivating reactive sulfate esters of carcinogenic arylmethanols. Biochem Biophys Res Commun. 1991 Dec 31;181(3):1294–1300. doi: 10.1016/0006-291x(91)92079-y. [DOI] [PubMed] [Google Scholar]
  23. Pearson W. R., Reinhart J., Sisk S. C., Anderson K. S., Adler P. N. Tissue-specific induction of murine glutathione transferase mRNAs by butylated hydroxyanisole. J Biol Chem. 1988 Sep 15;263(26):13324–13332. [PubMed] [Google Scholar]
  24. Pemble S. E., Taylor J. B. An evolutionary perspective on glutathione transferases inferred from class-theta glutathione transferase cDNA sequences. Biochem J. 1992 Nov 1;287(Pt 3):957–963. doi: 10.1042/bj2870957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pemble S., Schroeder K. R., Spencer S. R., Meyer D. J., Hallier E., Bolt H. M., Ketterer B., Taylor J. B. Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J. 1994 May 15;300(Pt 1):271–276. doi: 10.1042/bj3000271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pickett C. B., Lu A. Y. Glutathione S-transferases: gene structure, regulation, and biological function. Annu Rev Biochem. 1989;58:743–764. doi: 10.1146/annurev.bi.58.070189.003523. [DOI] [PubMed] [Google Scholar]
  27. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tan K. H., Meyer D. J., Gillies N., Ketterer B. Detoxification of DNA hydroperoxide by glutathione transferases and the purification and characterization of glutathione transferases of the rat liver nucleus. Biochem J. 1988 Sep 15;254(3):841–845. doi: 10.1042/bj2540841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tan K. L., Webb G. C., Baker R. T., Board P. G. Molecular cloning of a cDNA and chromosomal localization of a human theta-class glutathione S-transferase gene (GSTT2) to chromosome 22. Genomics. 1995 Jan 20;25(2):381–387. doi: 10.1016/0888-7543(95)80037-m. [DOI] [PubMed] [Google Scholar]
  30. Tirmenstein M. A., Reed D. J. Role of a partially purified glutathione S-transferase from rat liver nuclei in the inhibition of nuclear lipid peroxidation. Biochim Biophys Acta. 1989 Apr 6;995(2):174–180. doi: 10.1016/0167-4838(89)90077-0. [DOI] [PubMed] [Google Scholar]
  31. Townsend A. J., Goldsmith M. E., Pickett C. B., Cowan K. H. Isolation, characterization, and expression in Escherichia coli of two murine Mu class glutathione S-transferase cDNAs homologous to the rat subunits 3 (Yb1) and 4 (Yb2). J Biol Chem. 1989 Dec 25;264(36):21582–21590. [PubMed] [Google Scholar]

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