RADIATION-INDUCED KI-67 PROLIFERATION IN THE SMALL INTESTINE OF RATS
Introduction. It is known that Hiroshima and Nagasaki were target of the first atomic bombs in the history of mankind. As a result, the population of Japanese cities was exposed to internal and external irradiation. Numerous authors maintain that primary neutron-activated radionuclides are chemical elements 56Mn and 60Co. Herewith, 56Mn was determined the dominant role of neutrons induced by β-radiation during the first few hours after the atomic bombing. The systemic access in estimation of Кi-67 marker in radiosensitive small intestine defining the functional state and the interrelation of structural components serves as a combination of diagnostic criterion and prognosis. The objective of study. To assess the prognostic significance of Ki-67 antigen for detection of cell proliferative activity in the small intestine of rats exposed to low dose of β− and γ–radiation. Materials and methods. In experiment that held in February 2016, the male sex «Wistar» rats at 5 month old and in amount of 90, weighting approximately 270−350 g. Three groups were identified: 1) 56Mn which obtained by neutron activation of 100 mg MnO2 powder using the «Baikal−1» nuclear reactor with a neutrons fluence of 4×1014 n/cm²; 2) 60Co γ−rays; 3) control group. Necropsy of the animals were on the 3rd, 14th and 60th days after irradiation, then the small intestine removed, after which it was fixed in 10% formalin. Paraffin sections were dewaxed and rehydrated using the method of D.Sarkisov and Yu.Perov (1996). To visualize the immunohistochemical reaction, the DAB+(DAKO) system was used. The number of Ki-67-positive cells, taking into account the colored nuclei of any intensity, expressing the results in percent. All the presented data and results were expressed as mean (M), median (Me) and interquartile interval (IQR). Statistical comparisons were made by Kruskel-Wallis test (SPSS 2,0). A p<0,05 was considered statistically significant. Results. When comparing microscopic processes occurring in the rats small intestinal tissue after exposure to neutron-activated manganese dioxide and external irradiation, the most pronounced morphofunctional disorders which detected by the number of Ki-67-positive cells are noted in the later periods after 56Mn effect. The studied parameters of the small intestine have statistically significant differences in the control and irradiated animal groups (p<0,001). Conclusion. Morphofunctional disorders in the small intestine that result from internal and external irradiation are characterized by a change in the immunohistochemical indicator of Ki-67, indicative of cell proliferation in late terms. Comparing the level of Ki-67 antigen in the organ of various animal groups studied, a high level was observed in the late periods after exposure to neutron-activated manganese dioxide.
Darkhan E. Uzbekov ¹, http://orcid.org/0000–0003–4399–460X Dariya M. Shabdarbaeva ¹, http://orcid.org/0000–0001–9463–1935 Nailya Zh. Chaizhunusova ², http://orcid.org/0000–0002–6660–7118 Nurlan B. Sayakenov ¹, http://orcid.org/0000–0002–5082–7554 Saltanat E. Uzbekova ³, http://orcid.org/0000–0001–9006–120X Gauhar K. Amantaeva 4, http://orcid.org/0000–0002–8422–7936 Bakhyt Ruslanova ¹, http://orcid.org/0000–0003–3046–7077 Gulmira T. Aubakirova ¹, httрs://оrсіd.оrg/0000–0003–1997–4852 Ainur S. Abeuova ¹, https://orcid.org/0000–0002–1979–2605 Masaharu Hoshi 5, http://orcid.org/0000–0001–6978–0883 Gulnar M. Shalgumbayeva 6, http://orcid.org/0000-0003-3310-4490 ¹ Department of pathological anatomy and forensic medicine; ² Department of nutrition and hygienic disciplines; ³ Department of histology; 4 Department of microbiology; 6 Department of personalized medicine; Semey medical university, Semey, Kazakhstan, 5 Research institute for radiation biology and medicine, Hiroshima, Japan.
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Liu Z., Tian H., Jiang J., Yang Y., Tan S. et al. β–Arrestin–2 modulates radiation–induced intestinal crypt progenitor/stem cell injury. Cell Death and Differentiation. 2016. Vol. 23, N 9. pp. 1529–1541. 21. McMillan G. Is electric arc welding linked to manganism or Parkinson’s disease. Toxicology Review. 2005. Vol. 24, N 4. pp. 237–257. 22. Orlov M., Stepanenko V.F., Belukha I.G., Ohtaki M., Hoshi M. Calculation of contact beta–particle exposure of biological tissue from the residual radionucides in Hiroshima. Health Physics. 2014. Vol. 107, N 1. 44 p. 23. Qi Z., Chen Y.G. Regulation of intestinal stem cell fate specification. Science China Life Sciences. 2015. Vol. 58, N 6. pp. 570–578. 24. Roth J.A. Homeostatic and toxic mechanisms regulating manganese uptake, retention, and elimination. Biol. Res. 2006. Vol. 39, N 1. pp. 45–57. 25. Sasaki M.S., Endo S., Hoshi M., Nomura T. Neutron relative biological effectiveness in Hiroshima and Nagasaki atomic bomb survivors: a critical review. J. Radiat. Res. 2016. Vol. 57, N 6. pp. 583–595. 26. Shichijo K., Fujimoto N., Uzbekov D., Kairkhanova Y., Saimova A. et al. Internal exposure to neutron-activated 56Mn dioxide powder in Wistar rats – Part 2: pathological effects. Radiation and Environmental Biophysics. 2017. Vol. 56, N 1. pp. 55–61. 27. Stepanenko V., Rakhypbekov T., Otani K., Endo S., Satoh K. et al. Internal exposure to neutron-activated 56Mn dioxide powder in Wistar rats: part 1: dosimetry // Radiation and Environmental Biophysics. 2017. Vol. 56, N 1. pp. 47–54. 28. Tadbir A.A., Pardis S., Ashkavandi Z.J., Najvani A.D., Ashraf M.J. et al. Expression of Ki67 and CD105 as proliferation and angiogenesis markers in salivary gland tumors. Asian Pac. J. Cancer Prev. 2012. Vol. 13, N 10. pp. 5155–5159. 29. Tian H., Qian G.W., Li W., Chen F.F., Di J.H. et al. A critical role of Sp1 transcription factor in regulating the human Ki-67 gene expression. Tumour Biol. 2011. Vol. 32, N 2. pp. 273–283. 30. Uzbekov D., Hoshi M., Shichijo K., Chaizhunusova N., Shabdarbaeva D. et al. Comparative characteristics of histomorphologic changes in the small intestine of rats exposed to gamma– and neutron radiation. European Journal of Natural History. 2017. N 4. pp. 38-42 31. Uzbekov D.E., Hoshi M., Shichijo K., Chaizhunusova N.Zh., Shabdarbaeva D.M. et al. Radiation effects on morphofunctional state of the gastrointestinal tract (Literature review). Vestnik KazNMU [Bulletin Kaz NMU]. 2017. N 2. pp. 74–79. 32. Uzbekov D.E., Ilderbayev O.Z., Shabdarbaeva D.M., Sayakenov N.B., Uzbekova S.E. et al. Comparative characteristics of lipid peroxidation in small intestine at progeny irradiated rats. Vestnik KazNMU [Bulletin Kaz NMU]. 2016. N 3. pp. 148–152. 33. Uzbekov D.E., Shabdarbaeva D.M., Chaizhunusova N.Zh., Almisaev K.A., Uzbekova S.E. et al. Morphometric indicators of the small intestine of irradiated rats. Science & Healthcare. 2018. Vol. 20, N 3. pp. 5–19 34. Uzbekov D.E., Shichijo K., Fujimoto N., Shabdarbaeva D.M., Sayakenov N.B. et al. Radiation–induced apoptosis in the small intestine of rats. Science & Healthcare. 2017. N 3. pp. 32–44. 35. Van der Flier L.G., Clevers H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu. Rev. Physiol. 2009. Vol. 71. pp. 241–260. 36. Van Landeghem L., Santoro M.A., Krebs A.E., Mah A.T., Dehmer J.J. et al. Activation of two distinct Sox9-EGFP-expressing intestinal stem cell populations during crypt regeneration after irradiation. Am. J. Physiol. Gastrointest. Liver Physiol. 2012. Vol. 302, N 10. pp. 1111–1132 37. Wei L., Leibowitz B.J., Wang X., Epperly M., Greenberger J. et al. Inhibition of CDK4/6 protects against radiation-induced intestinal injury in mice. Journal of Clinical Investigation. 2016. Vol. 126, N 11. pp. 4076–4087 38. Williams J.P., Brown S.L., Georges G.E., Hauer-Jensen M., Hill R.P. et al. Animal models for medical countermeasures to radiation exposure. Radiat. Res. 2010. Vol. 173, N 4. pp. 557–578.
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Узбeкoв Д.E., Шaбдapбaeвa Д.М., Чaйжyнycoвa Н.Ж., Caякeнoв Н.Б., Узбeкoвa C.E., Aмaнтaeвa Г.K., Pycлaнoвa Б., Аубакирова Г.T., Aбeyoвa A.C., Xoши M., Шалгумбаева Г.М. Paдиaциoннo-индуциpoвaннaя пpoлифepaция КI-67 в тoнкoй кишкe кpыc // Наука и Здравоохранение. 2019. 1 (Т.21). С. 63-73. Uzbekov D.E., Shabdarbaeva D.M., Chaizhunusova N.Zh., Sayakenov N.B., Uzbekova S.E., Amantaeva G.K., Ruslanova B., Aubakirova G.T., Abeuova A.S., Hoshi M., Shalgumbayeva G.M. Radiation-induced KI-67 proliferation in the small intestine of rats. Nauka i Zdravookhranenie [Science & Healthcare]. 2019, (Vol.21) 1, pp. 63-73. Узбeкoв Д.E., Шaбдapбaeвa Д.М., Чaйжyнycoвa Н.Ж., Caякeнoв Н.Б., Узбeкoвa C.E., Aмaнтaeвa Г.K., Pycлaнoвa Б., Аубакирова Г.T., Aбeyoвa A.C., Xoши M., Шалгумбаева Г.М. Paдиaция әcepiнeн туындaғaн eгeуқұйpықтap жiңiшкe iшeгiндeгi КI-67 пpoлифepaцияcы // Ғылым және Денсаулық сақтау. 2019. 1 (Т.21). Б. 63-73.