Glutatyon S-transferaz (GST) izoenzimlerinin çeşitli kanser vakalarında araştırılması

Amaç: Bu çalışmada glutatyon S-transferaz (GST) izoenzimlerinden GST-a, GST-p, GST-m’nin kanser hastaları ve sağlıklı kontrollerde araştırılması amaçlarmıştır. Yöntem: 29-90 (57±13) yaşları arasında 66 (22 kadın, 44 erkek) kanserli hasta ile yaşları 23-59 (36±11) arasında 32 (16 kadın,16 erkek) sağlıklı kişide GST-a, GST-p ve kanserli hastalarda GST-m düzeyleri araştırıldı. Bulgular: Kanser vakalarında sırasıyla GST-a ve GST-p değerleri gastrointestinal sistem (GİS) kanserlerinde 5.60±3.74 ng/ml ve 37.24±10.74 ng/ml, karaciğer kanserinde 6.20±2.56 ng/ml ve 35.33±9.57 ng/ml, mide kanserinde 5.73±4.91 ng/ml ve 39.77±13.18 ng/ml, diğer kanserlerde 4.62±3.46 ng/ml ve 22.99±13.46 ng/ml, kontrol grubunda ise 4.77±3.24 ng/ml ve 23.47±9.97 ng/ml olarak bulundu. GST-m düzeyleri ise kanserli hasta grubunda % 59.52 oranında negatif olarak belirlendi. Tüm hasta grupları ile kontrol grubuna ait GST-a değerleri arasında istatistiksel olarak önemli bir fark bulunmazken, GST-p düzeyleri arasında önemli fark olduğu görüldü. Sonuç: GST-p nin özellikle gastrointestinal sistem, mide ve karaciğer kanserlerinin teşhisinde önemli bir belirleyici olabileceği, GST-m yokluğunun ise kanser açısından risk faktörü oluşturabileceği kanaatine varıldı.

İnvestigation of glutathion S-transferase (GST) isoenzymes in various cancer cases

Objective: In this study, investigation of serum GST-a, GST-p and GST-m of cancer patients and healthy controls were aimed. Methods: This study was carried out on 66 (22 female, 44 male) cancer patients aged 29 to 90 (57±13) years and 32 (16 female,16 male) healthy subjects aged 23 to 59 (36±11) years. Results: GST-a and GST-p levels of the patients with gastrointestinal tractus, liver, stomach and other type of cancers and of the control group were found to be 5.60±3.74 ng/ml and 37.24±10.74 ng/ml, 6.20±2.56 ng/ml and 35.33±9.57 ng/ml, 5.73±4.91 ng/ml and 39.77±13.18 ng/ml, 4.62±3.46 ng/ml and 22.99±13.46 ng/ml, 4.77±3.24 ng/ml and 23.47±9.97 ng/ml, respectively. The GST-m was negative on 59.52 % of the cancer patients. There was no significant difference between GST-a level of the control group and cancer patients whereas the increase of GST-p level of the patients with gastrointestinal tractus, liver and stomach cancer groups was statistically significant. Conclusion: GST-p a is marker for gastrointestinal tractus, stomach and the liver cancers, and it is thought that the absence of GST-m may create a risk for cancer.

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  • Tolman KG, Rej R. Liver function. In: Burtis CA, Ashwood ER, editors. Tietz textbook of clinical chemistry, 3th ed. Philadelphia: WB Saunders; 1999.
  • Balistreri WF, Rej R. Liver function. In: Burtis CA, Ashwood ER, editors. Tietz textbook of clinical chemistry, 2th ed. Philadelphia: WB Saunders; 1994.
  • Mannervik B. The isozymes of glutathione transferase. Adv Enzymol 1985; 57:357-417.
  • Marcus CJ, Habig WH, Jakoby WB. Glutathione transferase from human erythrocytes. Arch Biochem Biophys 1978;188:287-93.
  • Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. J Biol Chem 1974; 249:7130-9.
  • Di Ilio C, Aceto A, Bucciarelli T, Angelucci S, Felaco M, Grilli A, et al. Glutathione transferase isoenzymes from human radioimmunoassay for their measurement. Clin Chim Acta 1988;177:65-76.
  • Heckbert SR, Weiss NS, Hornung SK, Eaton DL, Motulsky AG. Glutathione S-transferase and epoxide hidrolase activity in human leukocytes in relation to risk of lung cancer and other smoking-related cancers. J Nat Cancer Institue1992;84:414-22.
  • Howie AF, Hayes JD, Beckett GJ. Purification of acidic glutathione S-tranferases from human lung, placenta and erythrocyte and the development of a specific radioimmunoassay for their measurement. Clin Chim Acta 1988;177:65-76.
  • Lewis AD, Forrester LM, Hayes JD, Wareing CJ, Carmichael J, Harris AL, et al. Glutathione S-transferase isoenzymes in human tumors and tumor derived cell lines. Brit J Cancer Letters 1989; 60:327-31.
  • Ommen BV, Bogaards JJP, Peters WHM, Blaauboer B, Bladeren PJV. Quantification of human hepatic glutathione S-transferases. Biochem J 1990;269:609-13.
  • McQuaid S, O'Brien A, Butler MR, Humphries P. Transcriptional activation of the glutathione S-transferase? gene in human ureteric and bladder carcinomas. Cancer Letters 1988; 39:209-16.
  • Nitsu Y, Takahashi Y, Saito T, Hirata Y, Arisato N, Maruyama H, KohgoY, et al. Serum glutathione-S-transferase-p as a tumor marker for gastrointestinal malignancies. Cancer 1989; 63:317-23.
  • Hayes PC, Hussey AJ, Keating J, Bouchier IAD, Wiliams R, Beckett GJ, et al. Glutathione S-transferase levels in autoimmune chronic active hepatitis: A more sensitive index of hepatocellular damage than aspartate transaminase. Clin Chim Acta 1988;172:211-6.
  • Howie AF, Douglas JG, Fergusson RJ, Beckett GJ. Measurements of glutathione S-tranferases Pi isoenzyme in plasma, a possible marker for adenocarcinoma of lung. Clin Chem 1990;36:453-6.
  • Lafuente A, Pujol F, Carretero P, Villa JP, Cuchi A. Human glutathione S-transferase m (GST-m) deficiency as a marker for the susceptibility to bladder and larynx cancer among smokers. Cancer Letters 1993;68:49-54.
  • Seidegard J, Pero RW, Markowitz MM, Roush G, Miller DG, Beattie EJ. Isoenzyme (s) of glutathione transferase (class Mü) as a marker for the susceptibility to lung cancer: A follow up study. Carcinogenesis1990;11:33-6.
  • Howie AF, Forrester LM, Glancey MJ, Schlager A, Powis G, Beckett GJ, et al. Glutathione S-transferase and glutathione peroxidase expression in normal and tumour human tissues. Carcinogenesis 1990;11:451-8.
  • Hepkit (GST-?) Biotrin International Ltd., Unit 1C, Stillorgan Industrial Park, Stillorgan, Co. Dublin, Ireland.
  • Mukit (GST-m) Biotrin International Ltd., Unit 1C, Stillorgan Industrial Park, Stillorgan, Co. Dublin, Ireland.
  • Glutathione S-transferase Pi GST Pi RIA. For the determination of GST Pi from plasma, serum and tumor tissue. Immundiagnostik GmbH, Wilhelmstr. 7, 64625 Bensheim, Germany.
  • Yann-Pyng ST, Hsieh T, Tu CD. The glutathione S-transferase D genes. J Biol Chem 1993;268:9737-46.
  • Iscan M, Coban T, Bulbul D, Eke BC, Aygormez S, Berberoglu U. Xenobiotic metabolizing and antioxidant enzymes in normal and neoplastic human breast tissue. Eur J Drug Metab Pharmacokinet 1988;23:497-500.
  • Lieshout EM, Haelst UJ, Wobbes T, Peters WH. Immunohistochemical localization of glutathione s-transferase alpha and pi in human esophagel squamous epithelium, Barrett’s epithelium and carcinoma. Jpn J Cancer Res 1999;90:530-5.
  • Hayes JD, Gilligan D, Chapman BJ, Beckett GJ. Purification of human hepatic GST and the development of a radioimmunoassay for their measurement in plasma. Clin Chim Acta 1983;134:107-21.
  • Beckett GJ, Foster GR, Hussey AJ, Oliveire DBG, Donovan JW, Prescott LF, et al. Plasma glutathione S-transferase and F Protein are more sensitive than alanine aminotransferase as markers of paracetamol (acetaminophen)-induced liver damage. Clin Chem 1989;35:2186-9.
  • Beckett GJ, Hussey AJ, Laing I, Howie AF, Hayes JD, Strange RC, et al. Measurement of glutathione S-transferase B1 in plasma after birth asphyxia: An early indication of hepatocellular damage. Clin Chem 1989;35:995-9.
  • Di Ilio C, Boccio GD, Aceto A, Casaccia R, Mucilli F, Federici G. Elevation of glutathione transferase activity in human lung tumour. Carcinogenesis 1988;9:335-40.
  • Eimoto H, Tsutsumi M, Nakajima A, Yamamoto K, Takashima Y, Maruyama H, et al. Expression of the glutathion S-transferase placental form in human lung carcinomas. Carcinogenesis 1988;9:2325-7.
  • Sato K, Satoh K, Tsuchida S, Hatayama I, Tamai K, Shen H. Glutathione S-transferases and (pre) neoplasia. Adv Cancer Res 1989;5:390-8.
  • Kobayashi Y. A study on diagnosis of oral squamous cell carcinoma (oral SCC) by glutathion S-transferase-pi (GST-pi). Kokubyo Gakkai Zasshi 1999;66:46-56.
  • Hu X, Herzog C, Zimniak P, Singh SV. Differential protection against benzo (a) pyrene-7,8-dihydrodiol-9,10-epoxide-induced DNA damage in HepG2 cells stably transfected with allelic variants of pi class human glutathione S-transferase. Cancer Res 1999;59:2358-62.
  • Lemos MC, Cabrita FJ, Silva HA, Vivan M, Placido F, Regateiro FJ. Genetic polymorphism of CYP2D6, GSTM1 and NAT2 and susceptibility to haematological neoplasias. Carcinogenesis 1999;20:1225-9.
  • *8th Asian-Pasific Congress of Clinical Biochemistry (11-16 October 1998, Kuala Lumpur, Malaysia)’de poster olarak sunulmuştur.