JOURNAL DESCRIPTION
The Medical Radiology and Radiation Safety journal ISSN 1024-6177 was founded in January 1956 (before December 30, 1993 it was entitled Medical Radiology, ISSN 0025-8334). In 2018, the journal received Online ISSN: 2618-9615 and was registered as an electronic online publication in Roskomnadzor on March 29, 2018. It publishes original research articles which cover questions of radiobiology, radiation medicine, radiation safety, radiation therapy, nuclear medicine and scientific reviews. In general the journal has more than 30 headings and it is of interest for specialists working in thefields of medicine¸ radiation biology, epidemiology, medical physics and technology. Since July 01, 2008 the journal has been published by State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. The founder from 1956 to the present time is the Ministry of Health of the Russian Federation, and from 2008 to the present time is the Federal Medical Biological Agency.
Members of the editorial board are scientists specializing in the field of radiation biology and medicine, radiation protection, radiation epidemiology, radiation oncology, radiation diagnostics and therapy, nuclear medicine and medical physics. The editorial board consists of academicians (members of the Russian Academy of Science (RAS)), the full member of Academy of Medical Sciences of the Republic of Armenia, corresponding members of the RAS, Doctors of Medicine, professor, candidates and doctors of biological, physical mathematics and engineering sciences. The editorial board is constantly replenished by experts who work in the CIS and foreign countries.
Six issues of the journal are published per year, the volume is 13.5 conventional printed sheets, 88 printer’s sheets, 1.000 copies. The journal has an identical full-text electronic version, which, simultaneously with the printed version and color drawings, is posted on the sites of the Scientific Electronic Library (SEL) and the journal's website. The journal is distributed through the Rospechat Agency under the contract № 7407 of June 16, 2006, through individual buyers and commercial structures. The publication of articles is free.
The journal is included in the List of Russian Reviewed Scientific Journals of the Higher Attestation Commission. Since 2008 the journal has been available on the Internet and indexed in the RISC database which is placed on Web of Science. Since February 2nd, 2018, the journal "Medical Radiology and Radiation Safety" has been indexed in the SCOPUS abstract and citation database.
Brief electronic versions of the Journal have been publicly available since 2005 on the website of the Medical Radiology and Radiation Safety Journal: http://www.medradiol.ru. Since 2011, all issues of the journal as a whole are publicly available, and since 2016 - full-text versions of scientific articles. Since 2005, subscribers can purchase full versions of other articles of any issue only through the National Electronic Library. The editor of the Medical Radiology and Radiation Safety Journal in accordance with the National Electronic Library agreement has been providing the Library with all its production since 2005 until now.
The main working language of the journal is Russian, an additional language is English, which is used to write titles of articles, information about authors, annotations, key words, a list of literature.
Since 2017 the journal Medical Radiology and Radiation Safety has switched to digital identification of publications, assigning to each article the identifier of the digital object (DOI), which greatly accelerated the search for the location of the article on the Internet. In future it is planned to publish the English-language version of the journal Medical Radiology and Radiation Safety for its development. In order to obtain information about the publication activity of the journal in March 2015, a counter of readers' references to the materials posted on the site from 2005 to the present which is placed on the journal's website. During 2015 - 2016 years on average there were no more than 100-170 handlings per day. Publication of a number of articles, as well as electronic versions of profile monographs and collections in the public domain, dramatically increased the number of handlings to the journal's website to 500 - 800 per day, and the total number of visits to the site at the end of 2017 was more than 230.000.
The two-year impact factor of RISC, according to data for 2017, was 0.439, taking into account citation from all sources - 0.570, and the five-year impact factor of RISC - 0.352.
Medical Radiology and Radiation Safety. 2024. Vol. 69. № 1
DOI:10.33266/1024-6177-2024-69-1-15-19
A.K. Chigasova1, 2, 3, M.V. Pustovalova1, 4, A.A. Osipov2, S.A. Korneva5,
P.S. Eremin6, E.I. Yashkina1, 2, M.A. Ignatov1, 2,Yu.A. Fedotov1, 2,
N.Yu. Vorobyeva1, 2, A.N. Osipov1, 2
Post-Radiation Changes in The Number of Phosphorylated H2ax
and Atm Protein Foci in Low Dose X-Ray Irradiated Human Mesenchymal Stem Cells
1 A.I. Burnazyan Federal Medical Biophysical Center, Moscow, Russia
2 N.N. Semenov Federal Research Center for Chemical Physics, Moscow, Russia
3 Institute of Biochemical Physics, Moscow, Russia
4 Moscow Institute of Physics and Technology, Moscow region, Dolgoprudny, Russia
5 M.V. Lomonosov Moscow State University, Moscow, Russia
6 National Medical Research Center of Rehabilitation and Balneology, Moscow, Russia
Contact person: N.Yu. Vorobyeva, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Aim: To study the patterns of changes in the number of foci of phosphorylated DNA double-strand break repair proteins H2AX (γH2AX) and ATM (pATM) in cultured human mesenchymal stem cells (MSCs) 1‒48 hours after exposure to X-ray radiation at doses of 40, 80, 160 and 250 mGy.
Material and methods: We used the primary culture of human MSCs, obtained from the collection of LLC “BioloT” (Russia). Cells were irradiated using a RUB RUST-M1 X-ray biological unit (Diagnostika-M LLC, Moscow, Russia) equipped with two X-ray emitters at a dose rate of 40 mGy/min (voltage of 100 kV, an anode current of 8 mA, and a 1.5 mm Al filter) and 4 °C temperature. To quantify the yield of γH2AX and pATM foci immunocytochemical staining was carried out with the use of γH2AX and pATM antibody respectively. Statistical analysis of the obtained data was carried out using the statistical software package Statistica 8.0 (StatSoft). To assess the significance of differences between samples, Student’s t-test was used.
Results: It was shown that the kinetics of changes in the number of γH2AX foci after irradiation at doses of 160 and 250 mGy and low (40‒80 mGy) doses are significantly different. In contrast to the significant (50‒60 %) decrease in the number of γH2AX foci observed
6 hours after irradiation at doses of 160 and 250 mGy, after irradiation at low doses, no significant decrease in γH2AX foci was observed at this time point. Analysis of the colocalization of γH2AX foci with pATM foci indicates that the mechanisms for maintaining a high number of γH2AX foci 24‒48 hours after low-dose irradiation are ATM independent. A hypothesis has been put forward to explain the phenomenon of maintaining the number of γH2AX foci 24‒48 hours after irradiation in low doses by replicative stress caused by stimulation of proliferation against the background of hyperproduction of free radicals, resulting in additional formation of DNA double-strand breaks and phosphorylation of H2AX by ATR kinase.
Keywords: mesenchymal stem cells, γH2AX, pATM, DNA double-strand breaks, X-ray radiation, low doses
For citation: Chigasova AK, Pustovalova MV, Osipov AA, Korneva SA, Eremin PS, Yashkina EI, Ignatov MA, Fedotov YuA, Vorobyeva NYu, Osipov AN. Post-Radiation Changes in The Number of Phosphorylated H2ax and Atm Protein Foci in Low Dose X-Ray Irradiated Human Mesenchymal Stem Cells. Medical Radiology and Radiation Safety. 2024;69(1):15–19. (In Russian). DOI:10.33266/1024-6177-2024-69-1-15-19
References
1. Mastrolia I., Foppiani E.M., Murgia A., Candini O., Samarelli A.V., Grisendi G., et al. Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review. Stem. Cells. Transl. Med. 2019;8;11:1135-1148. doi: 10.1002/sctm.19-0044.
2. Andrzejewska A., Lukomska B., Janowski M. Concise Review: Mesenchymal Stem Cells: From Roots to Boost. Stem. Cells. 2019;37;7:855-864. doi: 10.1002/stem.3016.
3. Smolinska A., Bzinkowska A., Rybkowska P., Chodkowska M., Sarnowska A. Promising Markers in the Context of Mesenchymal Stem/Stromal Cells Subpopulations with Unique Properties. Stem. Cells. Int. 2023;2023:1842958. doi: 10.1155/2023/1842958.
4. Zuk P.A., Zhu M., Mizuno H., Huang J., Futrell J.W., Katz A.J., et al. Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based Therapies. Tissue Engineering. 2001;7;2:211-228. doi: 10.1089/107632701300062859.
5. Oswald J., Boxberger S., Jorgensen B., Feldmann S., Ehninger G., Bornhauser M., et al. Mesenchymal Stem Cells Can Be Differentiated into Endothelial Cells in Vitro. Stem. Cells. 2004;22;3:377-84. doi: 10.1634/stemcells.22-3-377.
6. Пустовалова М.В., Грехова А.К., Осипов А.Н. Мезенхимальные стволовые клетки: эффекты воздействия ионизирующего излучения в малых дозах // Радиационная биология. Радиоэкология. 2018. Т.58, № 4. С. 352-362. doi: 10.1134/s086980311804015x. [Pustovalova M.V., Grekhova A.K., Osipov A.N. Mesenchymal Stem Cells: Effects of Exposure to Ionizing Radiation in Low Doses. Radiatsionnaya Biologiya. Radioekologiya = Radiation Biology. Radioecology. 2018;58;4:352-362. doi: 10.1134/s086980311804015x (In Russ.)].
7. Bushmanov A., Vorobyeva N., Molodtsova D., Osipov A.N. Utilization of DNA Double-Strand Breaks for Biodosimetry of Ionizing Radiation Exposure. Environmental Advances. 2022;8. doi: 10.1016/j.envadv.2022.100207.
8. Osipov A., Chigasova A., Yashkina E., Ignatov M., Fedotov Y., Molodtsova D., et al. Residual Foci of DNA Damage Response Proteins in Relation to Cellular Senescence and Autophagy in X-Ray Irradiated Fibroblasts. Cells. 2023;12;8. doi: 10.3390/cells12081209.
9. Belov O., Chigasova A., Pustovalova M., Osipov A., Eremin P., Vorobyeva N., et al. Dose-Dependent Shift in Relative Contribution of Homologous Recombination to DNA Repair after Low-LET Ionizing Radiation Exposure: Empirical Evidence and Numerical Simulation. Curr. Issues Mol. Biol. 2023;45;9:7352-73. doi: 10.3390/cimb45090465.
10. Georgoulis A., Vorgias C., Chrousos G., Rogakou E. Genome Instability and γH2AX. International Journal of Molecular Sciences. 2017;18;9. doi: 10.3390/ijms18091979.
11. Burma S., Chen B.P., Murphy M., Kurimasa A., Chen D.J. ATM Phosphorylates Histone H2AX in Response to DNA Double-Strand Breaks. J. Biol. Chem. 2001;276;45:42462-7. doi: 10.1074/jbc.C100466200.
12. Stiff T., O’Driscoll M., Rief N., Iwabuchi K., Lobrich M., Jeggo P.A. ATM and DNA-PK Function Redundantly to Phosphorylate H2AX after Exposure to Ionizing Radiation. Cancer Res. 2004;64;7:2390-6.
13. Zhou B.B., Elledge S.J. The DNA Damage Response: Putting Checkpoints in Perspective. Nature. 2000;408;6811:433-439. doi: 10.1038/35044005.
14. O’Driscoll M., Ruiz-Perez V.L., Woods C.G., Jeggo P.A., Goodship J.A. A Splicing Mutation Affecting Expression of Ataxia-Telangiectasia and Rad3-Related Protein (Atr) Results in Seckel Syndrome. Nature Genetics. 2003;33;4:497-501. doi: 10.1038/ng1129.
15. Reitsema T., Klokov D., Banath J.P., Olive P.L. DNA-PK Is Responsible for Enhanced Phosphorylation of Histone H2AX under Hypertonic Conditions. DNA Repair (Amst). 2005;4;10:1172-1181. doi: 10.1016/j.dnarep.2005.06.005.
16. Shibata A., Jeggo P.A. ATM’s Role in the Repair of DNA Double-Strand Breaks. Genes. 2021;12;9. doi: 10.3390/genes12091370.
17. Lee J.H., Paull T.T. Activation and Regulation of ATM Kinase Activity in Response to DNA Double-Strand Breaks. Oncogene. 2007;26;56:7741-7748. doi: 10.1038/sj.onc.1210872.
18. Kurz E.U., Lees-Miller S.P. DNA Damage-Induced Activation of ATM and ATM-Dependent Signaling Pathways. DNA Repair (Amst). 2004;3;8-9:889-900. doi: 10.1016/j.dnarep.2004.03.029.
19. Osipov A.N., Pustovalova M., Grekhova A., Eremin P., Vorobyova N., Pulin A., et al. Low Doses of X-Rays Induce Prolonged and ATM-Independent Persistence of GammaH2AX foci in Human Gingival Mesenchymal Stem Cells. Oncotarget. 2015;6;29:27275-87. doi: 10.18632/oncotarget.4739.
20. Грехова А.К., Еремин П.С., Осипов А.Н., Еремин И.И., Пустовалова М.В., Озеров И.В. и др. Замедленные процессы образования и деградации фокусов γН2ax в фибробластах кожи человека, подвергшихся воздействию рентгеновского излучения в малых дозах // Радиационная биология Радиоэкология. 2015;55(4):395-401. doi: 10.7868/s0869803115040037. [Grekhova A.K., Eremin P.S., Osipov A.N., Eremin I.I., Pustovalova M.V., Ozerov I.V., et al. Slow Processes of Formation and Degradation of γH2ax Foci in Human Skin Fibroblasts Exposed to Low-Dose X-Ray Radiation. Radiatsionnaya Biologiya. Radioekologiya = Radiation Biology. Radioecology. 2015;55;4:395-401. doi: 10.7868/s0869803115040037. (In Russ.)].
21. Biswas H., Makinwa Y., Zou Y. Novel Cellular Functions of ATR for Therapeutic Targeting: Embryogenesis to Tumorigenesis. International Journal of Molecular Sciences. 2023;24;14. doi: 10.3390/ijms241411684.
22. Suzuki K., Okada H., Yamauchi M., Oka Y., Kodama S., Watanabe M. Qualitative and Quantitative Analysis of Phosphorylated ATM Foci Induced by Low-Dose Ionizing Radiation. Radiat Res. 2006;165;5:499-504. doi: 10.1667/RR3542.1.
23. Large M., Reichert S., Hehlgans S., Fournier C., Rodel C., Rodel F. A Non-Linear Detection of Phospho-Histone H2AX in EA.hy926 Endothelial Cells Following Low-Dose X-Irradiation Is Modulated by Reactive Oxygen Species. Radiat Oncol. 2014;9:80. doi: 10.1186/1748-717X-9-80.
24. Baulch J.E., Craver B.M., Tran K.K., Yu L., Chmielewski N., Allen B.D., et al. Persistent Oxidative Stress in Human Neural Stem Cells Exposed to Low Fluences of Charged Particles. Redox Biology. 2015;5:24-32. doi: 10.1016/j.redox.2015.03.001.
25. Liang X., So Y.H., Cui J., Ma K., Xu X., Zhao Y., et al. 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;3:380-386.
26. Petermann E., Helleday T. Pathways of Mammalian Replication Fork Restart. Nature Reviews Molecular Cell Biology. 2010;11;10:683-687. doi: 10.1038/nrm2974.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The research was carried out with the support of the RNF (project No. 23-14-00078).
Contribution. Article was prepared with equal participation of the authors.
Article received: 20.10.2023. Accepted for publication: 27.11.2023.