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. 1993 Jun;67(6):1413–1417. doi: 10.1038/bjc.1993.262

Glutathione and glutathione S-transferases in Barrett's epithelium.

W H Peters 1, H M Roelofs 1, M P Hectors 1, F M Nagengast 1, J B Jansen 1
PMCID: PMC1968508  PMID: 8512826

Abstract

Glutathione content, enzyme activity and isoenzyme composition of glutathione S-transferases were assayed in normal and Barrett's esophageal epithelium of ten patients with Barrett's esophagus. In addition, gastric and duodenal specimens from the same patients were also investigated. Glutathione content, glutathione S-transferase enzyme activity as well as glutathione S-transferase pi content were all significantly lower in Barrett's epithelium as compared to normal esophageal mucosa. In contrast, glutathione S-transferase class alpha enzymes are markedly expressed in Barrett's epithelium, whereas only low amounts are present in normal esophageal epithelium. Glutathione and glutathione S-transferase composition in Barrett's epithelium show striking similarities with gastric epithelium, whereas duodenal epithelium is provided with considerable higher amounts of glutathione and glutathione S-transferases, except for levels of glutathione S-transferase class pi, which are lower. A significant negative correlation exists between glutathione S-transferase enzyme activity in the mucosa along the gastrointestinal tract, and the tumour incidence. Since glutathione and glutathione S-transferase are correlated with protection against cellular or cytogenetic damage, the low content of glutathione and glutathione S-transferases in the Barrett's esophagus may be a factor of relevance for the increased tumour risk in this tissue.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blot W. J., Devesa S. S., Kneller R. W., Fraumeni J. F., Jr Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA. 1991 Mar 13;265(10):1287–1289. [PubMed] [Google Scholar]
  2. Cameron A. J., Ott B. J., Payne W. S. The incidence of adenocarcinoma in columnar-lined (Barrett's) esophagus. N Engl J Med. 1985 Oct 3;313(14):857–859. doi: 10.1056/NEJM198510033131404. [DOI] [PubMed] [Google Scholar]
  3. Cameron A. J., Zinsmeister A. R., Ballard D. J., Carney J. A. Prevalence of columnar-lined (Barrett's) esophagus. Comparison of population-based clinical and autopsy findings. Gastroenterology. 1990 Oct;99(4):918–922. doi: 10.1016/0016-5085(90)90607-3. [DOI] [PubMed] [Google Scholar]
  4. Coles B., Ketterer B. The role of glutathione and glutathione transferases in chemical carcinogenesis. Crit Rev Biochem Mol Biol. 1990;25(1):47–70. doi: 10.3109/10409239009090605. [DOI] [PubMed] [Google Scholar]
  5. Fahey R. C., Newton G. L. Determination of low-molecular-weight thiols using monobromobimane fluorescent labeling and high-performance liquid chromatography. Methods Enzymol. 1987;143:85–96. doi: 10.1016/0076-6879(87)43016-4. [DOI] [PubMed] [Google Scholar]
  6. Habig W. H., Pabst M. J., Jakoby W. B. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974 Nov 25;249(22):7130–7139. [PubMed] [Google Scholar]
  7. Hirota M., Inoue M., Ando Y., Hirayama K., Morino Y., Sakamoto K., Mori K., Akagi M. Inhibition of stress-induced gastric injury in the rat by glutathione. Gastroenterology. 1989 Oct;97(4):853–859. doi: 10.1016/0016-5085(89)91488-1. [DOI] [PubMed] [Google Scholar]
  8. Howie A. F., Forrester L. M., Glancey M. J., Schlager J. J., Powis G., Beckett G. J., Hayes J. D., Wolf C. R. Glutathione S-transferase and glutathione peroxidase expression in normal and tumour human tissues. Carcinogenesis. 1990 Mar;11(3):451–458. doi: 10.1093/carcin/11.3.451. [DOI] [PubMed] [Google Scholar]
  9. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  10. Lash L. H., Hagen T. M., Jones D. P. Exogenous glutathione protects intestinal epithelial cells from oxidative injury. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4641–4645. doi: 10.1073/pnas.83.13.4641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Mårtensson J., Jain A., Stole E., Frayer W., Auld P. A., Meister A. Inhibition of glutathione synthesis in the newborn rat: a model for endogenously produced oxidative stress. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9360–9364. doi: 10.1073/pnas.88.20.9360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Peters W. H., Boon C. E., Roelofs H. M., Wobbes T., Nagengast F. M., Kremers P. G. Expression of drug-metabolizing enzymes and P-170 glycoprotein in colorectal carcinoma and normal mucosa. Gastroenterology. 1992 Aug;103(2):448–455. doi: 10.1016/0016-5085(92)90833-k. [DOI] [PubMed] [Google Scholar]
  15. Peters W. H., Kock L., Nagengast F. M., Kremers P. G. Biotransformation enzymes in human intestine: critical low levels in the colon? Gut. 1991 Apr;32(4):408–412. doi: 10.1136/gut.32.4.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Peters W. H., Kock L., Nagengast F. M., Roelofs H. M. Immunodetection with a monoclonal antibody of glutathione S-transferase mu in patients with and without carcinomas. Biochem Pharmacol. 1990 Feb 1;39(3):591–597. doi: 10.1016/0006-2952(90)90068-v. [DOI] [PubMed] [Google Scholar]
  17. Peters W. H., Nagengast F. M., Wobbes T. Glutathione S-transferases in normal and cancerous human colon tissue. Carcinogenesis. 1989 Dec;10(12):2371–2374. doi: 10.1093/carcin/10.12.2371. [DOI] [PubMed] [Google Scholar]
  18. Peters W. H., Wormskamp N. G., Thies E. Expression of glutathione S-transferases in normal gastric mucosa and in gastric tumors. Carcinogenesis. 1990 Sep;11(9):1593–1596. doi: 10.1093/carcin/11.9.1593. [DOI] [PubMed] [Google Scholar]
  19. Romano M., Razandi M., Raza A., Szabo S., Ivey J. Cysteamine protects gastric epithelial cell monolayers against drug induced damage: evidence for direct cellular protection by sulphydryl compounds. Gut. 1992 Jan;33(1):30–38. doi: 10.1136/gut.33.1.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Salim A. S. Sulfhydryls protect patients against complications of erosive gastritis. Dig Dis Sci. 1990 Nov;35(11):1436–1437. doi: 10.1007/BF01536754. [DOI] [PubMed] [Google Scholar]
  21. Seidegård J., Pero R. W., Markowitz M. M., Roush G., Miller D. G., Beattie E. J. Isoenzyme(s) of glutathione transferase (class Mu) as a marker for the susceptibility to lung cancer: a follow up study. Carcinogenesis. 1990 Jan;11(1):33–36. doi: 10.1093/carcin/11.1.33. [DOI] [PubMed] [Google Scholar]
  22. Spechler S. J., Robbins A. H., Rubins H. B., Vincent M. E., Heeren T., Doos W. G., Colton T., Schimmel E. M. Adenocarcinoma and Barrett's esophagus. An overrated risk? Gastroenterology. 1984 Oct;87(4):927–933. [PubMed] [Google Scholar]
  23. Strange R. C., Matharoo B., Faulder G. C., Jones P., Cotton W., Elder J. B., Deakin M. The human glutathione S-transferases: a case-control study of the incidence of the GST1 0 phenotype in patients with adenocarcinoma. Carcinogenesis. 1991 Jan;12(1):25–28. doi: 10.1093/carcin/12.1.25. [DOI] [PubMed] [Google Scholar]
  24. Wiencke J. K., Kelsey K. T., Lamela R. A., Toscano W. A., Jr Human glutathione S-transferase deficiency as a marker of susceptibility to epoxide-induced cytogenetic damage. Cancer Res. 1990 Mar 1;50(5):1585–1590. [PubMed] [Google Scholar]
  25. Zhong S., Howie A. F., Ketterer B., Taylor J., Hayes J. D., Beckett G. J., Wathen C. G., Wolf C. R., Spurr N. K. Glutathione S-transferase mu locus: use of genotyping and phenotyping assays to assess association with lung cancer susceptibility. Carcinogenesis. 1991 Sep;12(9):1533–1537. doi: 10.1093/carcin/12.9.1533. [DOI] [PubMed] [Google Scholar]
  26. van Ommen B., Bogaards J. J., Peters W. H., Blaauboer B., van Bladeren P. J. Quantification of human hepatic glutathione S-transferases. Biochem J. 1990 Aug 1;269(3):609–613. doi: 10.1042/bj2690609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. van Poppel G., de Vogel N., van Balderen P. J., Kok F. J. Increased cytogenetic damage in smokers deficient in glutathione S-transferase isozyme mu. Carcinogenesis. 1992 Feb;13(2):303–305. doi: 10.1093/carcin/13.2.303. [DOI] [PubMed] [Google Scholar]

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