Abstract
Glutathione S-transferase (GST) isoenzyme expression is altered in a variety of neoplasms and the enzymes are implicated in metabolism of carcinogens and resistance to drugs, including cisplatin. We have studied GST Alpha, Pi, Mu and microsomal isoenzyme expression by immunohistochemistry in normal and cryptorchid testes, intratubal germ cell neoplasia (ITGCN), seminoma and non-seminomatous germ cell tumours. In 16 stage II-IV malignant teratoma intermediate (MTI) both orchidectomy and post-treatment residual surgical masses were studied. All four isoenzymes were strongly expressed in Leydig and Sertoli cells. GST Pi was absent from normal spermatogonia but strongly expressed by the neoplastic germ cells of ITGCN and seminoma. GST Pi was strongly expressed in all elements of teratoma, irrespective of differentiation. There were no qualitative differences in expression between primary and post-chemotherapy metastases. GST Alpha expression in teratoma correlated with epithelial differentiation. GSTs may be important in normal spermatogenesis and protection of germ cells from teratogens and carcinogens. They may have a role in testicular tumour drug resistance but this role is not well defined. GST Pi is a new marker for ITGCN.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Batata M. A., Chu F. C., Hilaris B. S., Whitmore W. F., Golbey R. B. Testicular cancer in cryptorchids. Cancer. 1982 Mar 1;49(5):1023–1030. doi: 10.1002/1097-0142(19820301)49:5<1023::aid-cncr2820490528>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
- Batist G., Tulpule A., Sinha B. K., Katki A. G., Myers C. E., Cowan K. H. Overexpression of a novel anionic glutathione transferase in multidrug-resistant human breast cancer cells. J Biol Chem. 1986 Nov 25;261(33):15544–15549. [PubMed] [Google Scholar]
- Chasseaud L. F. The role of glutathione and glutathione S-transferases in the metabolism of chemical carcinogens and other electrophilic agents. Adv Cancer Res. 1979;29:175–274. doi: 10.1016/s0065-230x(08)60848-9. [DOI] [PubMed] [Google Scholar]
- Chong C., Logothetis C. J., von Eschenbach A., Ayala A., Samuels M. Orchiectomy in advanced germ cell cancer following intensive chemotherapy: a comparison of systemic to testicular response. J Urol. 1986 Dec;136(6):1221–1223. doi: 10.1016/s0022-5347(17)45290-6. [DOI] [PubMed] [Google Scholar]
- Dedon P. C., Borch R. F. Characterization of the reactions of platinum antitumor agents with biologic and nonbiologic sulfur-containing nucleophiles. Biochem Pharmacol. 1987 Jun 15;36(12):1955–1964. doi: 10.1016/0006-2952(87)90494-1. [DOI] [PubMed] [Google Scholar]
- Einhorn L. H., Williams S. D. Chemotherapy of disseminated testicular cancer. A random prospective study. Cancer. 1980 Sep 15;46(6):1339–1344. doi: 10.1002/1097-0142(19800915)46:6<1339::aid-cncr2820460607>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
- Fosså S. D., Aass N. Cisplatin-based chemotherapy does not eliminate the risk of a second testicular cancer. Br J Urol. 1989 May;63(5):531–534. doi: 10.1111/j.1464-410x.1989.tb05951.x. [DOI] [PubMed] [Google Scholar]
- Gondos B., Migliozzi J. A. Intratubular germ cell neoplasia. Semin Diagn Pathol. 1987 Nov;4(4):292–303. [PubMed] [Google Scholar]
- Grosshans K., Calvin H. I. Estimation of glutathione in purified populations of mouse testis germ cells. Biol Reprod. 1985 Dec;33(5):1197–1205. doi: 10.1095/biolreprod33.5.1197. [DOI] [PubMed] [Google Scholar]
- Hales B. F., Hachey C., Robaire B. The presence and longitudinal distribution of the glutathione S-transferases in rat epididymis and vas deferens. Biochem J. 1980 Jul 1;189(1):135–142. doi: 10.1042/bj1890135. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hayes J. D., Gilligan D., Chapman B. J., Beckett G. J. Purification of human hepatic glutathione S-transferases and the development of a radioimmunoassay for their measurement in plasma. Clin Chim Acta. 1983 Oct 31;134(1-2):107–121. doi: 10.1016/0009-8981(83)90189-4. [DOI] [PubMed] [Google Scholar]
- Hayes J. D., Mantle T. J. Use of immuno-blot techniques to discriminate between the glutathione S-transferase Yf, Yk, Ya, Yn/Yb and Yc subunits and to study their distribution in extrahepatic tissues. Evidence for three immunochemically distinct groups of transferase in the rat. Biochem J. 1986 Feb 1;233(3):779–788. doi: 10.1042/bj2330779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hayes J. D., McLellan L. I., Stockman P. K., Chalmers J., Beckett G. J. Glutathione S-transferases in man: the relationship between rat and human enzymes. Biochem Soc Trans. 1987 Aug;15(4):721–725. doi: 10.1042/bst0150721. [DOI] [PubMed] [Google Scholar]
- Hendry W. F., Barrett A., McElwain T. J., Wallace D. M., Peckham M. J. The role of surgery in the combined management of metastases from malignant teratomas of testis. Br J Urol. 1980 Feb;52(1):38–44. doi: 10.1111/j.1464-410x.1980.tb02917.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Hustin J., Collette J., Franchimont P. Immunohistochemical demonstration of placental alkaline phosphatase in various states of testicular development and in germ cell tumours. Int J Androl. 1987 Feb;10(1):29–35. doi: 10.1111/j.1365-2605.1987.tb00162.x. [DOI] [PubMed] [Google Scholar]
- Kramer R. A., Zakher J., Kim G. Role of the glutathione redox cycle in acquired and de novo multidrug resistance. Science. 1988 Aug 5;241(4866):694–697. doi: 10.1126/science.3399900. [DOI] [PubMed] [Google Scholar]
- Lawrence R. A., Burk R. F. Species, tissue and subcellular distribution of non Se-dependent glutathione peroxidase activity. J Nutr. 1978 Feb;108(2):211–215. doi: 10.1093/jn/108.2.211. [DOI] [PubMed] [Google Scholar]
- Li L. Y., Seddon A. P., Meister A., Risley M. S. Spermatogenic cell-somatic cell interactions are required for maintenance of spermatogenic cell glutathione. Biol Reprod. 1989 Feb;40(2):317–331. doi: 10.1095/biolreprod40.2.317. [DOI] [PubMed] [Google Scholar]
- Listowsky I., Abramovitz M., Homma H., Niitsu Y. Intracellular binding and transport of hormones and xenobiotics by glutathione-S-transferases. Drug Metab Rev. 1988;19(3-4):305–318. doi: 10.3109/03602538808994138. [DOI] [PubMed] [Google Scholar]
- Mannervik B., Alin P., Guthenberg C., Jensson H., Tahir M. K., Warholm M., Jörnvall H. Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7202–7206. doi: 10.1073/pnas.82.21.7202. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Mannervik B. The isoenzymes of glutathione transferase. Adv Enzymol Relat Areas Mol Biol. 1985;57:357–417. doi: 10.1002/9780470123034.ch5. [DOI] [PubMed] [Google Scholar]
- McCartney A. C., Paradinas F. J., Newlands E. S. Significance of the 'maturation' of metastases from germ cell tumours after intensive chemotherapy. Histopathology. 1984 May;8(3):457–467. doi: 10.1111/j.1365-2559.1984.tb02357.x. [DOI] [PubMed] [Google Scholar]
- Nakagawa K., Yokota J., Wada M., Sasaki Y., Fujiwara Y., Sakai M., Muramatsu M., Terasaki T., Tsunokawa Y., Terada M. Levels of glutathione S transferase pi mRNA in human lung cancer cell lines correlate with the resistance to cisplatin and carboplatin. Jpn J Cancer Res. 1988 Mar;79(3):301–304. doi: 10.1111/j.1349-7006.1988.tb01590.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rahilly M., Carder P. J., al Nafussi A., Harrison D. J. Distribution of glutathione S-transferase isoenzymes in human ovary. J Reprod Fertil. 1991 Nov;93(2):303–311. doi: 10.1530/jrf.0.0930303. [DOI] [PubMed] [Google Scholar]
- Russo A., Mitchell J. B., McPherson S., Friedman N. Alteration of bleomycin cytotoxicity by glutathione depletion or elevation. Int J Radiat Oncol Biol Phys. 1984 Sep;10(9):1675–1678. doi: 10.1016/0360-3016(84)90526-1. [DOI] [PubMed] [Google Scholar]
- Sato K. Glutathione transferases as markers of preneoplasia and neoplasia. Adv Cancer Res. 1989;52:205–255. doi: 10.1016/s0065-230x(08)60214-6. [DOI] [PubMed] [Google Scholar]
- Teaf C. M., Harbison R. D., Bishop J. B. Germ-cell mutagenesis and GSH depression in reproductive tissue of the F-344 rat induced by ethyl methanesulfonate. Mutat Res. 1985 Oct;144(2):93–98. doi: 10.1016/0165-7992(85)90009-0. [DOI] [PubMed] [Google Scholar]
- Teicher B. A., Holden S. A., Kelley M. J., Shea T. C., Cucchi C. A., Rosowsky A., Henner W. D., Frei E., 3rd Characterization of a human squamous carcinoma cell line resistant to cis-diamminedichloroplatinum(II). Cancer Res. 1987 Jan 15;47(2):388–393. [PubMed] [Google Scholar]
- Waxman D. J. Glutathione S-transferases: role in alkylating agent resistance and possible target for modulation chemotherapy--a review. Cancer Res. 1990 Oct 15;50(20):6449–6454. [PubMed] [Google Scholar]
- Yoganathan T., Eskild W., Hansson V. Investigation of detoxification capacity of rat testicular germ cells and Sertoli cells. Free Radic Biol Med. 1989;7(4):355–359. doi: 10.1016/0891-5849(89)90121-4. [DOI] [PubMed] [Google Scholar]
- Yoganathan T., Oyen O., Eskild W., Jahnsen T., Hansson V. Cellular localization and age dependent changes in mRNA for glutathione S-transferase-P in rat testicular cells. Biochem Int. 1989 Oct;19(4):667–672. [PubMed] [Google Scholar]