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Sitogenetik Hasar Böbrek Nakli Hastalarında Malignite Gelişimi İçin Bir Biyobelirteç Midir?

Yıl 2022, Cilt: 2 Sayı: 1, 6 - 13, 03.04.2022
https://doi.org/10.29228/HMJ.8

Öz

Amaç: Periferik kan lenfositlerinde mikronükleus (MN) oluşumu kanser gelişme riski için bir biyobelirteç olarak kullanılabilir. Bu çalışmada böbrek nakli hastalarında periferik lenfositlerde MN oluşumu ile malignite gelişimi arasındaki ilişkiyi değerlendirmeyi amaçladık.
Hastalar ve Yöntem: Bu çalışmaya böbrek nakli sonrası malignite gelişen 10 böbrek nakli hastası alındı. Yaş ve cinsiyet uyumlu böbrek nakil sonrası malignite gelişmeyen 15 böbrek nakli hastası böbrek nakli kontrol grubu olarak çalışmaya dahil edildi. Ayrıca yaş ve cinsiyet uyumlu 12 sağlıklı gönüllü de sağlıklı kontrol grubu olarak çalışmaya dahil edildi. MN analizi sitokinez blok MN analizi ile yapıldı.
Bulgular: Mononükleer hücrelerde MN sayısı malignitesi olan veya olmayan böbrek nakli hastalarında sağlıklı gönüllülerden anlamlı olarak daha yüksekti [sırasıyla 7.5 (2.0-11.0), 5.0 (0-12.0) ve 1.0 (0-9.0), p<0.001]. Benzer olarak binükleer hücrelerdeki MN sayısı malignitesi olan veya olmayan böbrek nakli hastalarında sağlıklı gönüllülerden anlamlı olarak daha yüksekti [sırasıyla 54.0 (8.0-199.0), 32.0 (0-182.0) ve 10.0 (2.00-29.00), p<0.001]. Aradaki fark istatistiksel olarak anlamlı olmamasına rağmen, hem mononükleer hücrelerde hem de binükleer hücrelerdeki MN sayısı malignitesi olan böbrek nakli hastalarında malignitesi olmayan böbrek nakli hastalarından daha yüksek saptandı.
Sonuç: Binükleer ve mononükleer hücrelerdeki artmış MN sayısı böbrek naklinden sonra malignite gelişimi için umut vaat eden bir biyobelirteç olabilir.

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Teşekkür

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Kaynakça

  • 1. Yang TC, Shu KH, Cheng CH, Wu MJ, Lian JD. Malignancy following renal transplantation. Zhonghua Yi Xue Za Zhi (Taipei) 1998; 61: 281-8.
  • 2. Morath C, Mueller M, Goldschmidt H, Schwenger V, Opelz G, Zeier M. Malignancy in renal transplantation. J Am Soc Nephrol 2004; 15: 1582-8.
  • 3. Fenech M. Cytokinesis-block micronucleus cytome assay. Nat Protoc 2007; 2: 1084-104.
  • 4. Bonassi S, Znaor A, Ceppi M, Lando C, Chang WP, Holland N, et al. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis 2007; 28: 625-31.
  • 5. Sekeroglu V, Sekeroglu ZA. [Micronucleus test for determining genotoxic damage]. Turk Hij Den Biyol Derg 2011; 68: 241-52. [Article in Turkish]
  • 6. Jagetia GC, Jayakrishnan A, Fernandes D, Vidyasagar MS. Evaluation of micronuclei frequency in the cultured peripheral blood lymphocytes of cancer patients before and after radiation treatment. Mutat Res 2001; 491: 9-16.
  • 7. Heddle JA, Hite M, Kirkhart B, Mavournin K, MacGregor JT, Newell GW, et al. The induction of micronuclei as a measure of genotoxicity. A report of the U.S. Environmental Protection Agency Gene-Tox Program. Mutat Res 1983; 123: 61-118.
  • 8. Farrow MG, McCarroll NE, Auletta AE. 1984 survey of genetic toxicology testing in industry, government and academic laboratories. J Appl Toxicol 1986; 6: 211-23.
  • 9. Yager JW, Sorsa M, Selvin S. Micronuclei in cytokinesis-blocked lymphocytes as an index of occupational exposure to alkylating cytostatic drugs. IARC Sci Publ 1988; 89: 213-6.
  • 10. Stopper H, Meysen T, Böckenförde A, Bahner U, Heidland A, Vamvakas S. Increased genomic damage in lymphocytes of patients before and after long-term maintenance hemodialysis therapy. Am J Kidney Dis 1999; 34: 433-7.
  • 11. Lizotti Cilião H, Batista de Oliveira Camargo-Godoy R, Mazzaron Barcelos GR, Zanuto A, Daher Alvares Delfino V, de Syllos Cólus IM. Long-term genotoxic effects of immunosuppressive drugs on lymphocytes of kidney transplant recipients. Mutat Res Genet Toxicol Environ Mutagen 2016; 806: 47-52.
  • 12. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604-12.
  • 13. Eastmond DA, Tucker JD. Identification of aneuploidy–inducing agents using cytokinesis–blocked human lymphocytes and an antikinetochore antibody. Environ. Mol. Mutgen 1989; 13: 34-43.
  • 14. Schuler M, Rupa DS, Easmond DA. A critical evaluation of centromeric labeling to distinguish micronuclei induced by chromosomal loss and breakage in vitro. Mutat Res 1997; 392: 81-95.
  • 15. Fenech M. The cytokinesis-block micronucleus teqnique and its application to genotoxicity studies in human populations. Environ Health Perspect 1993; 101: 101-7.
  • 16. Natarajan AT, Obe G. Mutagenicity. New York: Academic Press; 1982, 172-204 p.
  • 17. Buckton KE, Court-Brown WM, Smith PG. Lymphocyte survival in men treated with X-rays for ankylosing spondylitis. Nature 1967; 214: 470-3.
  • 18. El-Zein RA, Schabath MB, Etzel CJ, Lopez MS, Franklin JD, Spitz MR. Cytokinesis-blocked micronucleus assay as a novel biomarker for lung cancer risk. Cancer Res 2006; 66: 6449-56.
  • 19. El-Zein R, Vral A, Etzel CJ. Cytokinesis-blocked micronucleus assay and cancer risk assessment. Mutagenesis 2011; 26: 101-6.
  • 20. Shi YH, Wang BW, Tuokan T, Li QZ, Zhang YJ. Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance. Int J Clin Exp Pathol 2015; 8: 8426-32.
  • 21. Fucic A, Gamulin M, Katic J, Milic M, Druzhinin V, Grgić M. Genome damage in testicular seminoma patients seven years after radiotherapy. Int J Radiat Biol 2013; 89: 928-33.
  • 22. AlFaisal AH, Al-Ramahi IJ, Abdul-Hassan IA. Micronucleus frequency among Iraqi thyroid disorder patients. Comp Clin Path 2012; 23: 683-8.
  • 23. Kiraz A, Açmaz G, Uysal G, Unal D, Dönmez-Altuntas H. Micronucleus testing as a cancer detector: endometrial hyperplasia to carcinoma. Arch Gynecol Obstet 2016; 293: 1065-71.
  • 24. Mikhalevich LS, De Zwart FA, Perepetskaya GA, Chebotareva NV, Mikhalevich EA, Tates AD. Radiation effects in lymphocytes of children living in a Chernobyl contaminated region of Belarus. Int J Radiat Biol 2000; 76: 1377-85.
  • 25. Unal D, Kiraz A, Avci D, Tasdemir A, Unal TD, Cagli S, et al. Cytogenetic damage of radiotherapy in long-term head and neck cancer survivors. Int J Radiat Biol 2016; 92: 364-70.
  • 26. Oliveira VD, Zankl H, Rath T. Mutagenic and cytotoxic effects of immunosuppressive drugs on human lymphocyte cultures. Exp Clin Transplant 2004; 2: 273-9.
  • 27. Rath T, Oliveira-Frick V. Mutagenicity of immunosuppressive medications among renal transplant recipients. Am J Nephrol 2009; 30: 514-20.
  • 28. Driessens G, Harsan L, Robaye B, Waroquier D, Browaeys P, Giannakopoulos X, et al. Micronuclei to detect in vivo chemotherapy damage in a p53 mutated solid tumour. Br J Cancer 2003; 89: 727-9.
  • 29. Schlegel R, MacGregor JT, Everson RB. Assessment of cytogenetic damage by quantitation of micronuclei in human peripheral blood erythrocytes. Cancer Res 1986; 46: 3717-21.
  • 30. Arsoy NS, Neuss S, Wessendorf S, Bommer M, Viardot A, Schütz P, et al. Micronuclei in peripheral blood from patients after cytostatic therapy mainly arise ex vivo from persistent damage. Mutagenesis 2009; 24: 351-7.

Is Cytogenetıc Damage A Biomarker For The Risk Of Malignancy Development In Renal Transplantatıon Patients?

Yıl 2022, Cilt: 2 Sayı: 1, 6 - 13, 03.04.2022
https://doi.org/10.29228/HMJ.8

Öz

Objective: The micronucleus (MN) formation in the peripheral blood lymphocytes can be usable as a biomarker for the risk of cancer development. In this study, we aimed to evaluate the relationship between the MN formation in peripheral lymphocytes and the development of malignancy in renal transplant patients.
Materials and Methods: Ten renal transplant patients with post-transplant malignancy were included in the study. The control group with renal transplantation consisted of 15 age and sex matched renal transplant patients without post-transplant malignancy. The healthy control group consisted of 12 individuals who had similar age and sex ratios as the other two groups. The cytokinesis-block micronucleus (CBMN) assay was used for MN analysis.
Results: The number of MN in mononuclear cells was significantly higher in renal transplant patients with or without malignancy than in healthy controls [7.5 (2.0-11.0), 5.0 (0-12.0), and 1.0 (0-9.0), respectively, p<0.001]. Similarly, the number of MN in binuclear cells was significantly higher in renal transplant patients with or without malignancy than in healthy controls [54.0 (8.0-199.0), 32.0 (0-182.0), and 10.0 (2.00-29.00), respectively, p<0.001]. Although the difference was not statistically significant, the number of MN both in mononuclear cells and in binuclear cells was higher in renal transplant patients with malignancy than renal transplant patients without malignancy.
Conclusion: Increase in the number of MN in mononuclear and binuclear cells may be a promising biomarker for malignancy development after renal transplantation.

Kaynakça

  • 1. Yang TC, Shu KH, Cheng CH, Wu MJ, Lian JD. Malignancy following renal transplantation. Zhonghua Yi Xue Za Zhi (Taipei) 1998; 61: 281-8.
  • 2. Morath C, Mueller M, Goldschmidt H, Schwenger V, Opelz G, Zeier M. Malignancy in renal transplantation. J Am Soc Nephrol 2004; 15: 1582-8.
  • 3. Fenech M. Cytokinesis-block micronucleus cytome assay. Nat Protoc 2007; 2: 1084-104.
  • 4. Bonassi S, Znaor A, Ceppi M, Lando C, Chang WP, Holland N, et al. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis 2007; 28: 625-31.
  • 5. Sekeroglu V, Sekeroglu ZA. [Micronucleus test for determining genotoxic damage]. Turk Hij Den Biyol Derg 2011; 68: 241-52. [Article in Turkish]
  • 6. Jagetia GC, Jayakrishnan A, Fernandes D, Vidyasagar MS. Evaluation of micronuclei frequency in the cultured peripheral blood lymphocytes of cancer patients before and after radiation treatment. Mutat Res 2001; 491: 9-16.
  • 7. Heddle JA, Hite M, Kirkhart B, Mavournin K, MacGregor JT, Newell GW, et al. The induction of micronuclei as a measure of genotoxicity. A report of the U.S. Environmental Protection Agency Gene-Tox Program. Mutat Res 1983; 123: 61-118.
  • 8. Farrow MG, McCarroll NE, Auletta AE. 1984 survey of genetic toxicology testing in industry, government and academic laboratories. J Appl Toxicol 1986; 6: 211-23.
  • 9. Yager JW, Sorsa M, Selvin S. Micronuclei in cytokinesis-blocked lymphocytes as an index of occupational exposure to alkylating cytostatic drugs. IARC Sci Publ 1988; 89: 213-6.
  • 10. Stopper H, Meysen T, Böckenförde A, Bahner U, Heidland A, Vamvakas S. Increased genomic damage in lymphocytes of patients before and after long-term maintenance hemodialysis therapy. Am J Kidney Dis 1999; 34: 433-7.
  • 11. Lizotti Cilião H, Batista de Oliveira Camargo-Godoy R, Mazzaron Barcelos GR, Zanuto A, Daher Alvares Delfino V, de Syllos Cólus IM. Long-term genotoxic effects of immunosuppressive drugs on lymphocytes of kidney transplant recipients. Mutat Res Genet Toxicol Environ Mutagen 2016; 806: 47-52.
  • 12. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604-12.
  • 13. Eastmond DA, Tucker JD. Identification of aneuploidy–inducing agents using cytokinesis–blocked human lymphocytes and an antikinetochore antibody. Environ. Mol. Mutgen 1989; 13: 34-43.
  • 14. Schuler M, Rupa DS, Easmond DA. A critical evaluation of centromeric labeling to distinguish micronuclei induced by chromosomal loss and breakage in vitro. Mutat Res 1997; 392: 81-95.
  • 15. Fenech M. The cytokinesis-block micronucleus teqnique and its application to genotoxicity studies in human populations. Environ Health Perspect 1993; 101: 101-7.
  • 16. Natarajan AT, Obe G. Mutagenicity. New York: Academic Press; 1982, 172-204 p.
  • 17. Buckton KE, Court-Brown WM, Smith PG. Lymphocyte survival in men treated with X-rays for ankylosing spondylitis. Nature 1967; 214: 470-3.
  • 18. El-Zein RA, Schabath MB, Etzel CJ, Lopez MS, Franklin JD, Spitz MR. Cytokinesis-blocked micronucleus assay as a novel biomarker for lung cancer risk. Cancer Res 2006; 66: 6449-56.
  • 19. El-Zein R, Vral A, Etzel CJ. Cytokinesis-blocked micronucleus assay and cancer risk assessment. Mutagenesis 2011; 26: 101-6.
  • 20. Shi YH, Wang BW, Tuokan T, Li QZ, Zhang YJ. Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance. Int J Clin Exp Pathol 2015; 8: 8426-32.
  • 21. Fucic A, Gamulin M, Katic J, Milic M, Druzhinin V, Grgić M. Genome damage in testicular seminoma patients seven years after radiotherapy. Int J Radiat Biol 2013; 89: 928-33.
  • 22. AlFaisal AH, Al-Ramahi IJ, Abdul-Hassan IA. Micronucleus frequency among Iraqi thyroid disorder patients. Comp Clin Path 2012; 23: 683-8.
  • 23. Kiraz A, Açmaz G, Uysal G, Unal D, Dönmez-Altuntas H. Micronucleus testing as a cancer detector: endometrial hyperplasia to carcinoma. Arch Gynecol Obstet 2016; 293: 1065-71.
  • 24. Mikhalevich LS, De Zwart FA, Perepetskaya GA, Chebotareva NV, Mikhalevich EA, Tates AD. Radiation effects in lymphocytes of children living in a Chernobyl contaminated region of Belarus. Int J Radiat Biol 2000; 76: 1377-85.
  • 25. Unal D, Kiraz A, Avci D, Tasdemir A, Unal TD, Cagli S, et al. Cytogenetic damage of radiotherapy in long-term head and neck cancer survivors. Int J Radiat Biol 2016; 92: 364-70.
  • 26. Oliveira VD, Zankl H, Rath T. Mutagenic and cytotoxic effects of immunosuppressive drugs on human lymphocyte cultures. Exp Clin Transplant 2004; 2: 273-9.
  • 27. Rath T, Oliveira-Frick V. Mutagenicity of immunosuppressive medications among renal transplant recipients. Am J Nephrol 2009; 30: 514-20.
  • 28. Driessens G, Harsan L, Robaye B, Waroquier D, Browaeys P, Giannakopoulos X, et al. Micronuclei to detect in vivo chemotherapy damage in a p53 mutated solid tumour. Br J Cancer 2003; 89: 727-9.
  • 29. Schlegel R, MacGregor JT, Everson RB. Assessment of cytogenetic damage by quantitation of micronuclei in human peripheral blood erythrocytes. Cancer Res 1986; 46: 3717-21.
  • 30. Arsoy NS, Neuss S, Wessendorf S, Bommer M, Viardot A, Schütz P, et al. Micronuclei in peripheral blood from patients after cytostatic therapy mainly arise ex vivo from persistent damage. Mutagenesis 2009; 24: 351-7.
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Organ Nakli
Bölüm Araştırma Makaleleri
Yazarlar

Emel Mutlu 0000-0002-1008-2527

Aydın Ünal 0000-0002-5493-9908

Aslıhan Kiraz 0000-0001-7317-2717

Arzu Tasdemir 0000-0002-5183-6663

Tuba Dilay Ünal 0000-0003-3981-6026

İsmail Koçyiğit 0000-0002-6654-4727

Murat Sipahioğlu 0000-0003-3293-2104

Bülent Tokgöz 0000-0003-0880-3396

Yayımlanma Tarihi 3 Nisan 2022
Gönderilme Tarihi 19 Mart 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 2 Sayı: 1

Kaynak Göster

Vancouver Mutlu E, Ünal A, Kiraz A, Tasdemir A, Ünal TD, Koçyiğit İ, Sipahioğlu M, Tokgöz B. Sitogenetik Hasar Böbrek Nakli Hastalarında Malignite Gelişimi İçin Bir Biyobelirteç Midir?. HTD / HMJ. 2022;2(1):6-13.

e-ISSN: 2791-9935