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На протяжении всей жизни человек неизбежно подвергается воздействию низких доз ионизирующего излучения (ИИ) как фонового, так и в рамках медицинского лечения и диагностики, в ходе профессиональной деятельности, авиаперелетов и др. Эффекты, оказываемые низкими дозами ИИ, и риски отдаленных последствий этого воздействия, сегодня все больше привлекают внимание исследователей. С одной стороны, ученые указывают на развитие неблагоприятных последствий, в частности, накопление двухцепочечных разрывов ДНК, с другой, существуют исследования, демонстрирующие развитие таких явлений, как гормезис и адаптивный ответ. На основании этого существует предположение, что в диапазоне низких доз радиации может иметь место нелинейная зависимость эффектов от дозы облучения т.е. эффект не пропорционален полученной дозе, что согласуется с пороговой концепцией. Данному направлению исследований сегодня посвящено множество научных трудов. Особое внимание привлекают эффекты, оказываемые низкими дозами ИИ на мезенхимальные стромальные клетки (МСК) человека, поскольку они являются регенеративным резервом организма. Благодаря способности к самоподдержанию МСК могут длительное время находиться в организме и подвергаться нескольким раундам облучения, накапливая в себе происходящие изменения и передавая их следующим поколениям клеток, поскольку обладают потенциями к дифференцировке. Таким образом, изменения, произошедшее в МСК, отражаются на организме человека в целом. На основании всего вышеизложенного можно сделать вывод, что изучение эффектов, оказываемых низкими дозами радиации на мезенхимальные стромальные клетки человека, на сегодняшний день является актуальным направлением исследований.
адаптивный ответ, геномная нестабильность, мезенхимальные стромальные клетки, радиочувствительность, эффекты низких доз радиации, радиационный гормезис, радиорезистентность, эффект свидетеля
1. Squillaro T, Galano G, De Rosa R, Peluso G, Galderisi U. Concise Review: The Effect of Low-Dose Ionizing Radiation on Stem Cell Biology: A Contribution to Radiation Risk. Stem Cells. 2018;36(8):1146-1153. doihttps://doi.org/10.1002/stem.2836
2. Fazel R, Krumholz H, Wang Y. Exposure to Low-Dose Ionizing Radiation from Medical Imaging Procedures. J Vasc Surg. 2009;50(6):1526-1527. doihttps://doi.org/10.1016/j.jvs.2009.10.095
3. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann ICRP. 2007;37(2-4):1-332. doihttps://doi.org/10.1016/j.icrp.2007.10.003
4. Thurairajah K, Broadhead M, Balogh Z. Trauma and Stem Cells: Biology and Potential Therapeutic Implications. Int J Mol Sci. 2017;18(3):577. doihttps://doi.org/10.3390/ijms18030577
5. Ullah I, Subbarao R, Rho G. Human mesenchymal stem cells - current trends and future prospective. Biosci Rep. 2015;35(2). doihttps://doi.org/10.1042/bsr20150025
6. Aggarwal R, Lu J, J. Pompili V, Das H. Hematopoietic Stem Cells: Transcriptional Regulation, Ex Vivo Expansion and Clinical Application. Curr Mol Med. 2012;12(1):34-49. doihttps://doi.org/10.2174/156652412798376125
7. Wang Q, Sun B, Wang D et al. Murine Bone Marrow Mesenchymal Stem Cells Cause Mature Dendritic Cells to Promote T-Cell Tolerance. Scand J Immunol. 2008;68(6):607-615. doihttps://doi.org/10.1111/j.1365-3083.2008.02180.x
8. Spaggiari G, Capobianco A, Abdelrazik H, Becchetti F, Mingari M, Moretta L. Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood. 2008;111(3):1327-1333. doihttps://doi.org/10.1182/blood-2007-02-074997
9. Stagg J. Immune regulation by mesenchymal stem cells: two sides to the coin. Tissue Antigens. 2007;69(1):1-9. doihttps://doi.org/10.1111/j.1399-0039.2006.00739.x
10. Chen L, Tredget E, Wu P, Wu Y. Paracrine Factors of Mesenchymal Stem Cells Recruit Macrophages and Endothelial Lineage Cells and Enhance Wound Healing. PLoS One. 2008;3(4):e1886. doihttps://doi.org/10.1371/journal.pone.0001886
11. Dominici M, Le Blanc K, Mueller I et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-317. doihttps://doi.org/10.1080/14653240600855905
12. Gronthos S, Franklin D, Leddy H, Robey P, Storms R, Gimble J. Surface protein characterization of human adipose tissue-derived stromal cells. J Cell Physiol. 2001;189(1):54-63. doihttps://doi.org/10.1002/jcp.1138
13. Friedenstein A, Chailakhjan R, Lalykina K. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Prolif. 1970;3(4):393-403. doihttps://doi.org/10.1111/j.1365-2184.1970.tb00347.x
14. Bonab M, Alimoghaddam K, Talebian F, Ghaffari S, Ghavamzadeh A, Nikbin B. Aging of mesenchymal stem cell in vitro. BMC Cell Biol. 2006;7(1):14. doihttps://doi.org/10.1186/1471-2121-7-14
15. Rosland GV, Svendsen A, Torsvik A, Sobala E, McCormack E, Immervoll H, Mysliwietz J, Tonn JC, Goldbrunner R, Lonning PE et al. Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res. 2009; 69(1):5331-5339 doi:https://doi.org/10.1158/0008-5472.CAN-08-4630.
16. Chen G, Yue A, Ruan Z, Yin Y, Wang R, Ren Y, Zhu L. Monitoring the biology stability of human umbilical cord-derived mesenchymal stem cells during long-term culture in serum-free medium. Cell Tissue Bank. 2014; 15(1):513-521 doi:https://doi.org/10.1007/s10561-014-9420-6.
17. Lomax ME, Folkes LK, O'Neill P. Biological consequences of radiation- induced DNA damage: relevance to radiotherapy. Clin. Oncol. (R. Coll. Radiol.). 2013;25(1):578-585. doi:https://doi.org/10.1016/j.clon.2013.06.007.
18. Mao Z, Bozzella M, Seluanov A, Gorbunova V. Comparison of non- homologous end joining and homologous recombination in human cells. DNA Repair (Amst.). 2008;7(1):1765-1771. doi:https://doi.org/10.1016/j.dnarep.2008.06.018.
19. Solokov M., Neumman R. Human embryonic stem cell responses to ionizing radiation exposures: current state of knowledge and future challenges. Stem Cells Int. 2012;2012:579104 doi:https://doi.org/10.1155/2012/579104.
20. Prise KM, Saran A. Concise review: stem cell effects in radiation risk. Stem Cells. 2011;29(1):1315-1321. doi:https://doi.org/10.1002/stem.690.
21. Delacote F, Lopez BS. Importance of the cell cycle phase for the choice of the appropriate DSB repair pathway, for genome stability maintenance: the trans-S double-strand break repair model. Cell Cycle. 2008;7(1):33-38. doi:https://doi.org/10.4161/cc.7.1.5149.
22. Islam MS, Stemig ME., Takahashi Y, Hui SK. Radiation response of mesenchymal stem cells derived from bone marrow and human pluripotent stem cells. J. Radiat. Res. 2015;56(1):269-277. doi:https://doi.org/10.1093/jrr/rru098.
23. Nicolay N et al. Mesenchymal stem cells are resistant to carbon ion radiotherapy. Oncotarget. 2015;6(1):2076-2087. doi:https://doi.org/10.18632/oncotarget.2857.
24. Oliver L et al. Differentiation-related response to DNA breaks in human mesenchymal stem cells. Stem Cells. 2013;31(1):800-807. doi:https://doi.org/10.1002/stem.1336.
25. Tsvetkova A et al. γH2AX, 53BP1 and Rad51 protein foci changes in mesenchymal stem cells during prolonged X-ray irradiation. Oncotarget. 2017;8(1):64317-64329. doi:https://doi.org/10.18632/oncotarget.19203.
26. Wu P et al. Early passage mesenchymal stem cells display decreased radiosensitivity and increased DNA repair activity. Stem Cells Transl. Med. 2017;6(1):1504-1514. doi:https://doi.org/10.1002/sctm.15-0394. PMID: 28544661.
27. Aypar U, Morgan W, Baulch J. Radiation-induced genomic instability: are epigenetic mechanisms the missing link? Int. J. Radiat. Biol. 2011;87(1):179-191. doi:https://doi.org/10.3109/09553002.2010.522686.
28. Meyer B et al. Histone H3 lysine 9 acetylation obstructs ATM activation and promotes ionizing radiation sensitivity in normal stem cells. Stem Cell Rep. 2016;7(1):1013-1022. doi:https://doi.org/10.1016/j.stemcr.2016.11.004.
29. Armstrong C et al. DNMTs are required for delayed genome instability caused by radiation. Epigenetics. 2012;7(1):892-902. doi:https://doi.org/10.4161/epi.21094.
30. Tang F, Loke W. Molecular mechanisms of low dose ionizing radiation-induced hormesis, adaptive responses, radioresistance, bystander effects, and genomic instability. Int J Radiat Biol. 2015;91(1):13-27. doi:https://doi.org/10.3109/09553002.201 4.937510.
31. Liu S. On radiation hormesis expressed in the immune system. Critical Reviews in Toxicology. 2003;33(1):431-441. doi:https://doi.org/10.1080/713611045.
32. Liang X, So YH, Cui J, Ma K, Xu X, Zhao Y, Cai L, Li W. The low-dose ionizing radiation stimulates cell proliferation via activation of the MAPK/ERK pathway in rat cultured mesenchymal stem cells. Journal of Radiation Research. 2011;52(1):380-386. doi:https://doi.org/10.1269/jrr.10121.
33. Truong K, Bradley S, Baginski B, Wilson J, Medlin D, Zheng L, Wilson R, Rusin M, Takacs E, Dean D. The effect of well-characterized, very low-dose x-ray radiation on fibroblasts. PLoS One. 2018;13(1):e0190330. doi:https://doi.org/10.1371/journal.pone.0190330
34. Bernal A, Dolinoy D, Huang D, Skaar D, Weinhouse C, Jirtle R. Adaptive radiation-induced epigenetic alterations mitigated by antioxidants. Journal of the Federation of American Societies for Experimental Biology. 2013;27(1):665-671. doi:https://doi.org/10.1096/fj.12-220350.
35. Grdina D, Murley J, Miller R, Mauceri H, Sutton H, Thirman M, Li J, Woloschak G, Weichselbaum R. A Manganese Superoxide Dismutase (SOD2)-Mediated Adaptive Response. Radiation Research. 2013;179(1):115-124. doi:https://doi.org/10.1667/RR3126.2.
36. Takahashi A, Ohnishi K, Asakawa I, Kondo N, Nakagawa H, Yonezawa M, Tachibana A, Matsumoto H, Ohnishi T. Radiation response of apoptosis in C57BL/6N mouse spleen after whole-body irradiation. International Journal of Radiation Biology. 2001;77(1): 939-945. doi:https://doi.org/10.1080/09553000110062873.
37. Morgan W, Day J, Kaplan M, McGhee E, Limoli C. Genomic instability induced by ionizing radiation. Radiation Research.1996;146(1):247-258.
38. Pampfer S, Streffer C. Increased chromosome aberration levels in cells from mouse fetuses after zygote X-irradiation. Radiation Biology.1989;55(1):85-92. doi:https://doi.org/10.1080/09553008914550091.
39. Smith L, Nagar S, Kim G, Morgan W. Radiation-induced genomic instability: radiation quality and dose response. Health Physics. 2003;85(1):23-29. doi:https://doi.org/10.1097/00004032-200307000-00006.
40. McIlrath J, Lorimore S, Coates P, Wright E. Radiation induced genomic instability in immortalized haemopoietic stem cells. International Journal of Radiation Biology.2003;79(1):27-34.
41. El-Osta, A. The rise and fall of genomic methylation in cancer. Leukemia. 2004;18(1):233-237 doi:https://doi.org/10.1038/sj.leu.2403218.
42. Matsumoto H, Hamada N, Takahashi A, Kobayashi Y, Ohnishi T. Vanguards of paradigm shift in radiation biology: radiation-induced adaptive and bystander responses. Journal of Radiation Research. 2007;48(1):97-106. doi:https://doi.org/10.1269/jrr.06090.
43. Klokov D, Criswell T, Leskov K, Araki S, Mayo L, Boothman D. IR- inducible clusterin gene expression: a protein with potential roles in ionizing radiation-induced adaptive responses, genomic instability, and bystander effects. Mutation Research. 2004;568(1):97-110. doi:https://doi.org/10.1016/j.mrfmmm.2004.06.049.
44. Moore S, Marsden S, Macdonald D, Mitchell S, Folkard M, Michael B, Goodhead D, Prise K, Kadhim M. Genomic instability in human lymphocytes irradiated with individual charged particles: involvement of tumor necrosis factor alpha in irradiated cells but not bystander cells. Radiation Research. 2005;163(1):183-190. doi:https://doi.org/10.1667/rr3298.
45. Marchese M, Hall E. Encapsulated iodine-125 in radiation oncology. II. Study of the dose rate effect on potentially lethal damage repair (PLDR) using mammalian cell cultures in plateau phase. American Journal of Clinical Oncology.1984;7(1):613-616.
46. Boreham D, Mitchel R. DNA lesions that signal the induction of radioresistance and DNA repair in yeast. Radiation Research. 1991;128(1):19-28.
47. Piccinini A, Midwood K. DAMPening inflammation by modulating TLR signalling. Mediator inflamm. 2010;2010: 672395 doi:https://doi.org/10.1155/2010/672395.
48. Ilnytskyy Y, Koturbash I, Kovalchuk O. Radiation-induced bystander effects in vivo are epigenetically regulated in a tissue-specific manner. Environ. Mol. Mutagen. 2009;50(2):105-113. doi:https://doi.org/10.1002/em.20440.
49. Yahyapour R, Amini P, Rezapoor S, Rezaeyan A, Farhood B, Cheki M, Fallah H, Najafi M. Targeting of Inflammation for Radiation Protection and Mitigation. Curr. Mol. Pharmacol. 2018;11(3):203-210. doi:https://doi.org/10.2174/1874467210666171108165641.
50. Zhang J, Liu J, Ren J, Sun T, Mitochondrial DNA induces inflammation and increases TLR9/NF-B expression in lung tissue. Int J Mol Med. 2014;33(4):817-824. doi:https://doi.org/10.3892/ijmm.2014.1650.
51. Yahyapour R, Motevaseli E, Rezaeyan A, Abdollahi H, Farhood B, Cheki M, Najafi M, Villa V. Mechanisms of Radiation Bystander and Non-Targeted Effects: Implications to Radiation Carcinogenesis and Radiotherapy. Curr Radiopharm. 2018;11(1):34-45. doi:https://doi.org/10.2174/1874471011666171229123130.
52. Kumar Jella K, Rani S, O'Driscoll L, McClean B, Byrne H, Lyng F. Exosomes are involved in mediating radiation induced by- stander signaling in human keratinocyte cells. Radiat. Res. 2014;181(2):138-145. doi:https://doi.org/10.1667/RR13337.1.
53. Xu S, Wang, J, Ding N, Hu W, Zhang X, Wang B, Hua J, Wei W, Zhu Q. Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect. RNA. Biol. 2015;12(12):1355-1363. doi:https://doi.org/10.1080/15476286.2015.1100795.
54. Ma Y, Zhang L, Rong S, Qu H, Zhang Y, Chang D, Pan H, Wang W. Relation between gastric cancer and protein oxidation, DNA damage, and lipid peroxidation. Oxid. Med. Cell Lon-gev. 2013;2013:543760. doi:https://doi.org/10.1155/2013/543760.
55. Chaudhry M. Real-time PCR analysis of micro-RNA expression in ionizing radiation-treated cells. Cancer Biother. Radiopharm. 2009;24(1):49-56. doi:https://doi.org/10.1089/cbr.2008.0513.
56. Findik D, Song Q, Hidaka H, Lavin M. Protein kinase A inhibitors enhance radiation induced apoptosis. J. Cellular Bio-chem. 1995;57(1):12-21. doi:https://doi.org/10.1002/jcb.240570103.
57. Dong C, He M, Ren R, Xie Y, Yuan D, Dang B, Li W, Shao C. Role of the MAPK pathway in the observed bystander effect in lymphocytes co-cultured with macrophages irradiated with gamma-rays or carbon ions. Life Sci. 2015;127(1):19-25. doi:https://doi.org/10.1016/j.lfs.2015.02.017.
58. Moon K, Stukenborg G, Keim J, Theodorescu D. Cancer incidence after localized therapy for prostate cancer. Cancer. 2006;107(5):991-998. doi:https://doi.org/10.1002/cncr.22083.
59. Marozik P, Mothersill C, Seymour C.B, Mosse I, Melnov S. Bystander effects induced by serum from survivors of the Chernobyl accident. Exp. Hematol., 2007;35(4):55-63. doi:https://doi.org/10.1016/j.exphem.2007.01.029.
60. Halimi M, Parsian H, Asghari S, Sariri R, Moslemi D, Yeganeh F, Zabihi E. Clinical translation of human microRNA-21 as a potential biomarker for exposure to ionizing radiation. Transl. Res. 2014;163(6):578-584. doi:https://doi.org/10.1016/j.trsl.2014.01.009.
