Skip to main content
NCBI home page
International Journal of Experimental Pathology logoLink to International Journal of Experimental Pathology
. 1995 Aug;76(4):271–276.

Expression of xenobiotic metabolizing enzymes in tumours of the urinary bladder.

G I Murray 1, V E Taylor 1, J A McKay 1, R J Weaver 1, S W Ewen 1, W T Melvin 1, M D Burke 1
PMCID: PMC1997184  PMID: 7547441

Abstract

The cytochromes P450, epoxide hydrolase and glutathione S-transferases are several of the major groups of enzymes involved in the metabolism of xenobiotics and these enzymes may have a role in influencing the response of tumours to anti-cancer drugs. In this study the cell specific expression of individual xenobiotic metabolizing enzymes has been investigated using immunohistochemistry in primary transitional cell tumours of the urinary bladder. The cytochromes P450 CYP1A, CYP2C and CYP3A, were present in 68, 28 and 68% of tumours respectively and the expression of CYP1A correlated with bladder tumour grade (P = 0.03). Epoxide hydrolase was identified in 84% of tumours while the alpha, mu and pi forms of glutathione S-transferase were expressed in 56, 72 and 52% of tumours respectively. In normal bladder epoxide hydrolase and glutathione S-transferase pi were the main enzymes expressed while there was no expression of CYP2C.

Full text

PDF
271

Images in this article

274Figure 1
on p.274
274Figure 2
on p.274
274Figure 3
on p.274

Selected References

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

  1. Ahn H., Lee E., Kim K., Lee C. Effect of glutathione and its related enzymes on chemosensitivity of renal cell carcinoma and bladder carcinoma cell lines. J Urol. 1994 Jan;151(1):263–267. doi: 10.1016/s0022-5347(17)34929-7. [DOI] [PubMed] [Google Scholar]
  2. Board P., Coggan M., Johnston P., Ross V., Suzuki T., Webb G. Genetic heterogeneity of the human glutathione transferases: a complex of gene families. Pharmacol Ther. 1990;48(3):357–369. doi: 10.1016/0163-7258(90)90054-6. [DOI] [PubMed] [Google Scholar]
  3. Cairns J., Wright C., Cattan A. R., Hall A. G., Cantwell B. J., Harris A. L., Horne C. H. Immunohistochemical demonstration of glutathione S-transferases in primary human breast carcinomas. J Pathol. 1992 Jan;166(1):19–25. doi: 10.1002/path.1711660105. [DOI] [PubMed] [Google Scholar]
  4. Campbell J. A., Corrigall A. V., Guy A., Kirsch R. E. Immunohistologic localization of alpha, mu, and pi class glutathione S-transferases in human tissues. Cancer. 1991 Mar 15;67(6):1608–1613. doi: 10.1002/1097-0142(19910315)67:6<1608::aid-cncr2820670623>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
  5. Czerwinski M., McLemore T. L., Gelboin H. V., Gonzalez F. J. Quantification of CYP2B7, CYP4B1, and CYPOR messenger RNAs in normal human lung and lung tumors. Cancer Res. 1994 Feb 15;54(4):1085–1091. [PubMed] [Google Scholar]
  6. Di Ilio C., Aceto A., Bucciarelli T., Angelucci S., Felaco M., Grilli A., Zezza A., Tenaglia R., Federici G. Glutathione transferase isoenzymes in normal and neoplastic human kidney tissue. Carcinogenesis. 1991 Aug;12(8):1471–1475. doi: 10.1093/carcin/12.8.1471. [DOI] [PubMed] [Google Scholar]
  7. Foster J. R., Idle J. R., Hardwick J. P., Bars R., Scott P., Braganza J. M. Induction of drug-metabolizing enzymes in human pancreatic cancer and chronic pancreatitis. J Pathol. 1993 Apr;169(4):457–463. doi: 10.1002/path.1711690412. [DOI] [PubMed] [Google Scholar]
  8. Gonzalez F. J., Gelboin H. V. Role of human cytochromes P450 in the metabolic activation of chemical carcinogens and toxins. Drug Metab Rev. 1994;26(1-2):165–183. doi: 10.3109/03602539409029789. [DOI] [PubMed] [Google Scholar]
  9. Graham M. A., Riley R. J., Kerr D. J. Drug metabolism in carcinogenesis and cancer chemotherapy. Pharmacol Ther. 1991;51(2):275–289. doi: 10.1016/0163-7258(91)90083-x. [DOI] [PubMed] [Google Scholar]
  10. Green J. A., Robertson L. J., Clark A. H. Glutathione S-transferase expression in benign and malignant ovarian tumours. Br J Cancer. 1993 Aug;68(2):235–239. doi: 10.1038/bjc.1993.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kawajiri K., Fujii-Kuriyama Y. P450 and human cancer. Jpn J Cancer Res. 1991 Dec;82(12):1325–1335. doi: 10.1111/j.1349-7006.1991.tb01800.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lafuente A., Giralt M., Cervello I., Pujol F., Mallol J. Glutathione-S-transferase activity in human superficial transitional cell carcinoma of the bladder. Comparison with healthy controls. Cancer. 1990 May 1;65(9):2064–2068. doi: 10.1002/1097-0142(19900501)65:9<2064::aid-cncr2820650929>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  13. Le Blanc G. A., Waxman D. J. Interaction of anticancer drugs with hepatic monooxygenase enzymes. Drug Metab Rev. 1989;20(2-4):395–439. doi: 10.3109/03602538909103550. [DOI] [PubMed] [Google Scholar]
  14. McKay J. A., Weaver R. J., Murray G. I., Ewen S. W., Melvin W. T., Burke M. D. Localization of microsomal epoxide hydrolase in normal and neoplastic human kidney. J Histochem Cytochem. 1995 Jun;43(6):615–620. doi: 10.1177/43.6.7769232. [DOI] [PubMed] [Google Scholar]
  15. Murray G. I., Barnes T. S., Sewell H. F., Ewen S. W., Melvin W. T., Burke M. D. The immunocytochemical localisation and distribution of cytochrome P-450 in normal human hepatic and extrahepatic tissues with a monoclonal antibody to human cytochrome P-450. Br J Clin Pharmacol. 1988 Apr;25(4):465–475. doi: 10.1111/j.1365-2125.1988.tb03331.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Murray G. I., Paterson P. J., Weaver R. J., Ewen S. W., Melvin W. T., Burke M. D. The expression of cytochrome P-450, epoxide hydrolase, and glutathione S-transferase in hepatocellular carcinoma. Cancer. 1993 Jan 1;71(1):36–43. doi: 10.1002/1097-0142(19930101)71:1<36::aid-cncr2820710107>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  17. Murray G. I., Weaver R. J., Paterson P. J., Ewen S. W., Melvin W. T., Burke M. D. Expression of xenobiotic metabolizing enzymes in breast cancer. J Pathol. 1993 Mar;169(3):347–353. doi: 10.1002/path.1711690312. [DOI] [PubMed] [Google Scholar]
  18. Nebert D. W. Drug-metabolizing enzymes in ligand-modulated transcription. Biochem Pharmacol. 1994 Jan 13;47(1):25–37. doi: 10.1016/0006-2952(94)90434-0. [DOI] [PubMed] [Google Scholar]
  19. Nelson D. R., Kamataki T., Waxman D. J., Guengerich F. P., Estabrook R. W., Feyereisen R., Gonzalez F. J., Coon M. J., Gunsalus I. C., Gotoh O. The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol. 1993 Jan-Feb;12(1):1–51. doi: 10.1089/dna.1993.12.1. [DOI] [PubMed] [Google Scholar]
  20. Ranganathan S., Tew K. D. Immunohistochemical localization of glutathione S-transferases alpha, mu, and pi in normal tissue and carcinomas from human colon. Carcinogenesis. 1991 Dec;12(12):2383–2387. doi: 10.1093/carcin/12.12.2383. [DOI] [PubMed] [Google Scholar]
  21. Seidegård J., DePierre J. W. Microsomal epoxide hydrolase. Properties, regulation and function. Biochim Biophys Acta. 1983 Dec 29;695(3-4):251–270. doi: 10.1016/0304-419x(83)90014-8. [DOI] [PubMed] [Google Scholar]
  22. Singh S. V., Roberts B., Gudi V. A., Ruiz P., Awasthi Y. C. Immunohistochemical localization, purification, and characterization of human urinary bladder glutathione S-transferases. Biochim Biophys Acta. 1991 Aug 6;1074(3):363–370. doi: 10.1016/0304-4165(91)90086-v. [DOI] [PubMed] [Google Scholar]
  23. Terrier P., Townsend A. J., Coindre J. M., Triche T. J., Cowan K. H. An immunohistochemical study of pi class glutathione S-transferase expression in normal human tissue. Am J Pathol. 1990 Oct;137(4):845–853. [PMC free article] [PubMed] [Google Scholar]
  24. Tew K. D. Glutathione-associated enzymes in anticancer drug resistance. Cancer Res. 1994 Aug 15;54(16):4313–4320. [PubMed] [Google Scholar]
  25. Thrasher J. B., Crawford E. D. Current management of invasive and metastatic transitional cell carcinoma of the bladder. J Urol. 1993 May;149(5):957–972. doi: 10.1016/s0022-5347(17)36270-5. [DOI] [PubMed] [Google Scholar]
  26. Tsuchida S., Sato K. Glutathione transferases and cancer. Crit Rev Biochem Mol Biol. 1992;27(4-5):337–384. doi: 10.3109/10409239209082566. [DOI] [PubMed] [Google Scholar]
  27. Weaver R. J., Dickins M., Burke M. D. Cytochrome P450 2C9 is responsible for hydroxylation of the naphthoquinone antimalarial drug 58C80 in human liver. Biochem Pharmacol. 1993 Oct 5;46(7):1183–1197. doi: 10.1016/0006-2952(93)90467-b. [DOI] [PubMed] [Google Scholar]
  28. Xu B. H., Gupta V., Singh S. V. Mitomycin C sensitivity in human bladder cancer cells: possible role of glutathione and glutathione transferase in resistance. Arch Biochem Biophys. 1994 Jan;308(1):164–170. doi: 10.1006/abbi.1994.1023. [DOI] [PubMed] [Google Scholar]

Articles from International Journal of Experimental Pathology are provided here courtesy of Wiley

RESOURCES