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.
Issues journals
Medical Radiology and Radiation Safety. 2022. Vol. 67. № 5
DOI: 10.33266/1024-6177-2022-67-5-52-58
L.I. Moskvicheva, S.V. Medvedev, L.V. Bolotina
POSSIBILITIES OF MODERN RADIATION THERAPY
IN PATIENTS WITH PANCREATIC CANCER
P.A. Hertsen Moscow Oncology Research Institute, Moscow, Russia
Contact person: Liudmila I. Moskvicheva, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Introduction: Until now, malignant neoplasms of the pancreas remain a very important oncological problem, which is determined by the long subclinical course of the disease, the primary diagnosis of most tumors already at advanced stages, as well as the pronounced effect of this pathology on the functional status and overall quality of life of patients. No more than a quarter of patients with pancreatic cancer can be operated on. The remaining significant part of patients receive palliative anticancer treatment and/or symptomatic therapy.
Purpose: The purpose of this work is to analyze the possibilities of modern methods of radiation therapy in patients with pancreatic cancer based on the analysis of scientific sources of the Internet resource National Center for Biotechnology Information.
Sections: This article describes the role of preoperative chemoradiotherapy using 3D-conformal techniques in patients with localized and borderline resectable pancreatic cancer, the effectiveness of chemoradiotherapy as an adjuvant component, and the possibilities of this method in patients with locally advanced disease. The advantages of modern radiotherapy regimens are demonstrated: with modulated intensity or volume intensity modulation by arches, stereotaxic technique, proton and adaptive MR-guided radiation therapy. The international experience of brachytherapy in patients with pancreatic cancer was analyzed.
Conclusion: Modern methods of radiotherapy are widely used in clinical practice for the treatment of patients with adenogenic pancreatic cancer. The implementation of various options for radiation or chemoradiation therapy can significantly increase the survival rates of patients with localized, borderline resectable and locally advanced process, the frequency of achieving local tumor control and its duration, as well as improve the quality of life of patients by reducing the severity of abdominal pain syndrome. Constant improvement in the technique of radiation treatment contributes to a natural decrease in the frequency of early and late radiation reactions.
Keywords: pancreatic cancer, radiation therapy, brachytherapy, proton beam therapy, intensity modulated radiation therapy, stereotactic body radiotherapy, adaptive magnetic resonance image-guided radiation therapy
For citation: Moskvicheva LI, Medvedev SV, Bolotina LV. Possibilities of Modern Radiation Therapy in Patients with Pancreatic Cancer. Medical Radiology and Radiation Safety. 2022;67(5):52–58. (In Russian). DOI: 10.33266/1024-6177-2022-67-5-52-58
References
1. Состояние онкологической помощи населению России в 2019 году / Под ред. Каприна А.Д., Старинского В.В., Шахзадовой А.О. М: МНИОИ им. П.А.Герцена, 2020. 239 с. [The State of Oncological Care to the Population of Russia in 2019. Ed. Kaprin A.D., Starinskiy V.V., Shakhzadova A.O. Moscow Publ., 2020. 239 p. (In Russ.)].
2. McGuigan A., Kelly P., Turkington R.C., Jones C., Coleman H.G., McCain R.S. Pancreatic Cancer: A Review of Clinical Diagnosis, Epidemiology, Treatment and Outcomes. World J. Gastroenterol. 2018;24;43:4846-4861. DOI: 10.3748/wjg.v24.i43.4846.
3. Москвичева Л.И., Петров Л.О., Сидоров Д.В. Возможности современных методов абляции при нерезектабельном местно-распространенном раке поджелудочной железы // Исследования и практика в медицине. 2018. Т.5, № 2 С. 86-99. [Moskvicheva L.I., Petrov L.O., Sidorov D.V. The Possibilities of Modern Methods of Ablation in Non-Resectable Locally Advanced Pancreatic Cancer. Issledovaniya i Praktika v Meditsine = Research’n Practical Medicine Journal. 2018;5;2:86-99 (In Russ.)]. DOI: 10.17709/2409-2231-2018-5-2-10.
4. Москвичева Л.И., Болотина Л.В. Возможности химиотерапии у больных местно-распространенным и метастатическим аденогенным раком поджелудочной железы // Исследования и практика в медицине. 2020. Т.7, № 4. С. 118-134. [Moskvicheva L.I., Bolotina L.V. Possibilities of Chemotherapy in Patients with Locally Advanced and Metastatic Adenogenic Pancreatic Cancer. Issledovaniya i Praktika v Meditsine = Research’n Practical Medicine Journal. 2020;7;4:118-134
(In Russ.)]. DOI: 10.17709/2409-2231-2020-7-4-10.
5. Robin T.P., Goodman K.A. Radiation Therapy in the Management of Pancreatic Adenocarcinoma: Review of Current Evidence and Future Opportunities. Chin. Clin. Oncol. 2017;6;3:28. DOI: 10.21037/cco.2017.06.12.
6. Hong T.S., Ryan D.P., Borger D.R., Blaszkowsky L.S., Yeap B.Y., Ancukiewicz M., et al. A Phase 1/2 and Biomarker Study of Preoperative Short Course Chemoradiation with Proton Beam Therapy and Capecitabine Followed by Early Surgery for Resectable Pancreatic Ductal Adenocarcinoma. Int. J. Radiat. Oncol. Biol. Phys. 2014;89;4:830-838. DOI: 10.1016/j.ijrobp.2014.03.034.
7. Hall W.A., Goodman K.A. Radiation Therapy for Pancreatic Adenocarcinoma, a Treatment Option that must Be Considered in the Management of a Devastating Malignancy. Radiat. Oncol. 2019;14;1:114. DOI: 10.1186/s13014–019–1277–1.
8. Golcher H., Brunner T.B., Witzigmann H., Marti L., Bechstein W.O., Bruns C., et al. Neoadjuvant Chemoradiation Therapy with Gemcitabine/Cisplatin and Surgery Versus Immediate Surgery in Resectable Pancreatic Cancer: Results of the First Prospective Randomized Phase II Trial. Strahlenther Onkol. 2015;191;1:7-16. DOI: 10.1007/s00066–014–0737–7.
9. Versteijne E., Suker M., Groothuis K., Akkermans-Vogelaar J.M., Besselink M.G., Bonsing B.A., et al. Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial. J. Clin. Oncol. 2020;38;16:1763-1773. DOI: 10.1200/JCO.19.02274.
10. Hsu C.C., Herman J.M., Corsini M.M., Winter J.M., Callister M.D., Haddock M.G., et al. Adjuvant Chemoradiation for Pancreatic Adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic Collaborative Study. Ann. Surg. Oncol. 2010;17;4:981-990. DOI: 10.1245/s10434–009–0743–7.
11. Hammel P., Huguet F., van Laethem J.L., Goldstein D., Glimelius B., Artru P., et al. Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial. JAMA. 2016;315;17:1844-1853. DOI: 10.1001/jama.2016.4324.
12. Медведев С.В., Ткачев С.И. Рак поджелудочной железы // Терапевтическая радиология. Национальное руководство. Гл. 15 / Под ред. ак. Каприна А.Д., Мардынского Ю.С. М.: ГЭОТАР-Медиа, 2018. С. 155-159. [Medvedev S.V., Tkachev S.I. Pancreatic Cancer. Terapevticheskaya Radiologiya. Natsionalnoye Rukovodstvo = Therapeutic Radiology. National Leadership. Ch. 15. Ed. Kaprin A.D., Mardynskiy Yu.S. Moscow, GEOTAR-Media Publ., 2018. P. 155-159 (In Russ.)].
13. Krishnan S., Chadha A.S., Suh Y., Chen H.C., Rao A., Das P., et al. Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation. Int. J. Radiat. Oncol. Biol. Phys. 2016;94;4:755-765. DOI: 10.1016/j.ijrobp.2015.12.003.
14. Ткачев С.И., Медведев С.В., Знаткова Я.Р., Романов Д.С., и др. Возможности стереотаксической лучевой терапии при паллиативном лечении больных раком поджелудочной железы // Вопросы онкологии. 2015, Т.61, № 1. С. 121–124. [Tkachev S.I., Medvedev S.V., Znatkova Ya.R., Romanov D.S., et al. The Possibilities of Stereotactic Radiotherapy in Palliative Treatment of Patients with Pancreatic Cancer. Voprosy Onkologii = Problems in Oncology. 2015;61;1:121–124 (In Russ.)].
15. Reyngold M., Parikh P., Crane C.H. Ablative Radiation Therapy for Locally Advanced Pancreatic Cancer: Techniques and Results. Radiat. Oncol. 2019;14;1:95. DOI: 10.1186/s13014–019–1309–x.
16. Zhong J., Patel K., Switchenko J., Cassidy R.J., Hall W.A., Gillespie T., et al. Outcomes for Patients with Locally Advanced Pancreatic Adenocarcinoma Treated with Stereotactic Body Radiation Therapy Versus Conventionally Fractionated Radiation. Cancer. 2017;15;123;18:3486-3493. DOI: 10.1002/cncr.30706.
17. Dohopolski M.J., Glaser S.M., Vargo J.A., Balasubramani G.K., Beriwal S. Stereotactic Body Radiotherapy for Locally-Advanced Unresectable Pancreatic Cancer-Patterns of Care and Overall Survival. J. Gastrointest Oncol. 2017;8;5:766-777. DOI: 10.21037/jgo.2017.08.04.
18. Jung J., Yoon S.M., Park J.H., Seo D.W., Lee S.S., Kim M.H., et al. Stereotactic Body Radiation Therapy for Locally Advanced Pancreatic Cancer. PLoS One. 2019;14;4:e0214970. DOI: 10.1371/journal.pone.0214970.
19. Zhong J., Switchenko J., Behera M., Kooby D., Maithel S.K., McDonald M.W., et al. Chemotherapy with or Without Definitive Radiation Therapy in Inoperable Pancreatic Cancer. Ann Surg. Oncol. 2018;25;4:1026-1033. DOI: 10.1245/s10434–017–6322–4.
20. Herman J.M., Chang D.T., Goodman K.A., Dholakia A.S., Raman S.P., Hacker-Prietz A., et al. Phase 2 Multi-Institutional Trial Evaluating Gemcitabine and Stereotactic Body Radiotherapy for Patients with Locally Advanced Unresectable Pancreatic Adenocarcinoma. Cancer. 2015;121;7:1128-1137. DOI: 10.1002/cncr.29161.
21. Nichols R.C.Jr., George T.J., Zaiden R.A.Jr, Awad Z.T., Asbun H.J., Huh S., et al. Proton Therapy with Concomitant Capecitabine for Pancreatic and Ampullary Cancers is Associated with a Low Incidence of Gastrointestinal Toxicity. Acta. Oncol. 2013;52;3:498-505. DOI: 10.3109/0284186X.2012.762997.
22. Thompson R.F., Mayekar S.U., Zhai H., Both S., Apisarnthanarax S., Metz J.M., et al. A Dosimetric Comparison of Proton and Photon Therapy in Unresectable Cancers of the Head of Pancreas. Med. Phys. 2014;41;8:081711. DOI: 10.1118/1.4887797.
23. Hiroshima Y., Fukumitsu N., Saito T., Numajiri H., Murofushi K.N., Ohnishi K., et al. Concurrent Chemoradiotherapy Using Proton Beams for Unresectable Locally Advanced Pancreatic Cancer. Radiother Oncol. 2019;136:37-43. DOI: 10.1016/j.radonc.2019.03.012.
24. Henke L., Kashani R., Yang D., Zhao T., Green O., Olsen L., et al. Simulated Online Adaptive Magnetic Resonance-Guided Stereotactic Body Radiation Therapy for the Treatment of Oligometastatic Disease of the Abdomen and Central Thorax: Characterization of Potential Advantages. Int. J. Radiat. Oncol. Biol. Phys. 2016;96;5:1078-1086. DOI: 10.1016/j.ijrobp.2016.08.036.
25. Bohoudi O., Bruynzeel A.M.E., Senan S., Cuijpers J.P., Slotman B.J., Lagerwaard F.J., Palacios M.A. Fast and Robust Online Adaptive Planning in Stereotactic MR-Guided Adaptive Radiation Therapy (SMART) for Pancreatic Cancer. Radiother Oncol. 2017;125;3:439-444. DOI: 10.1016/j.radonc.2017.07.028.
26. Rudra S., Jiang N., Rosenberg S.A., Olsen J.R., Roach M.C., Wan L., et al. Using Adaptive Magnetic Resonance Image-Guided Radiation Therapy for Treatment of Inoperable Pancreatic Cancer. Cancer Med. 2019;8;5:2123-2132. DOI: 10.1002/cam4.2100.
27. Jia S.N., Wen F.X., Gong T.T., Li X., Wang H.J., Sun Y.M., Yang Z.C. A Review on the Efficacy and Safety of Iodine-125 Seed Implantation in Unresectable Pancreatic Cancers. Int. J. Radiat. Biol. 2020;96;3:383-389. DOI: 10.1080/09553002.2020.1704300.
28. Sun X., Lu Z., Wu Y., Min M., Bi Y., Shen W., et al. An Endoscopic Ultrasonography-Guided Interstitial Brachytherapy Based Special Treatment-Planning System for Unresectable Pancreatic Cancer. Oncotarget. 2017;8;45:79099-79110. DOI: 10.18632/oncotarget.15763.
29. Zhang K., Liao A., Jiang P., Jiang Y., Ji Z. Expert Consensus Workshop Report: Guideline for Three-Dimensional Printing Template-Assisted Computed Tomography-Guided 125i Seeds Interstitial Implantation Brachytherapy. J. Cancer Res. Ther. 2017;13;4:607-612. DOI: 10.4103/jcrt.JCRT_412_17.
30. Guo J.H., Hu X.K., Teng G.J. Radioactive Seed Implantation Therapy Technology: Problems and Development. Natl. Med. J. China. 2017;97:1444–1445.
31. Gai B., Zhang F. Chinese Expert Consensus on Radioactive 125I Seeds Interstitial Implantation Brachytherapy For Pancreatic Cancer. J. Cancer Res. Ther. 2018;14;7:1455-1462. DOI: 10.4103/jcrt.JCRT_96_18.
32. Folkert M.R., Gottumukkala S., Nguyen N.T., Taggar A., Sur R.K. Review of Brachytherapy Complications - Upper Gastrointestinal Tract. Brachytherapy. 2021;20;5:1005-1013. DOI: 10.1016/j.brachy.2020.11.010.
33. Han Q., Deng M., Lv Y., Dai G. Survival of Patients with Advanced Pancreatic Cancer after Iodine125 Seeds Implantation Brachytherapy: A Meta-Analysis. Medicine (Baltimore). 2017;96;5:e5719. DOI: 10.1097/MD.0000000000005719.
34. Chi Z., Chen L., Huang J., Jiang N., Zheng Q., Huang N., Yang W. A Novel Combination of Percutaneous Stenting with Iodine-125 Seed Implantation and Chemotherapy for the Treatment of Pancreatic Head Cancer with Obstructive Jaundice. Brachytherapy. 2021;20;1:218-225. DOI: 10.1016/j.brachy.2020.09.009.
35. Bhutani M.S., Cazacu I.M., Luzuriaga Chavez A.A., Singh B.S., Wong F.C.L., et al. Novel EUS-Guided Brachytherapy Treatment of Pancreatic Cancer with Phosphorus-32 Microparticles: First United States Experience. VideoGIE. 2019;4;5:223-225. DOI: 10.1016/j.vgie.2019.02.009.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The study had no sponsorship.
Contribution. Article was prepared with equal participation of the authors.
Article received: 20.06.2022. Accepted for publication: 25.08.2022.
Medical Radiology and Radiation Safety. 2022. Vol. 67. № 4
Effect of Dose Uncertainty on the Assessment of Radiation Risks of Solid Cancer Incidence
in a Cohort of Russian Participants in the Elimination of the Consequences of the Accident
at the Chernobyl NPP
V.K. Ivanov, S.Yu. Chekin, M.A. Maksioutov, A.I. Gorski, S.V.Karpenko , K.A. Tumanov, V.V. Kashcheev, A.M. Korelo,
E.V. Kochergina
Tsyb Medical Radiological Research Center, Obninsk, Russia
Contact person: Sergei Yurievich Chekin, e-mail:
This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Purpose: Investigation of the influence of the possible uncertainty of exposure doses of Russian participants in the liquidation of the consequences of the Chernobyl accident on the assessment of radiation risks of the incidence of solid cancer in this cohort.
Material and methods: Epidemiological and dosimetric data on a cohort of Russian participants in the liquidation of the consequences of the accident at the Chernobyl NPP, registered in the National Radiation and Epidemiological Register (NRER), are used as initial data for assessing radiation risks. The assessment of radiation risks is carried out by the statistical method of maximum likelihood in the framework of a linear non-threshold model of excess relative risk. Uncertainties in the liquidator’s exposure dose in the adopted risk assessment method are considered in the form of two error models. Dose estimates based on data from individual dosimeters are characterized by a classical model of measurement errors. In the case of estimates of unknown individual doses from group dosimetry data or group route doses, the Berkson assignment error model is used.
Results: A method for assessing radiation risks has been developed, accounting for the uncertainty in dose estimates, based on the observed likelihood function. When taking into account the uncertainty of estimates of individual doses in the cohort of Russian liquidators, the estimate of the coefficient of the excess relative rate per dose unit (ERR/Gy) for the incidence of solid malignancies decreases by 7%, compared with the estimate obtained directly from the doses registered in the NRER database. The ERR/Gy estimate derived from the doses recorded in the NRER database was 0.69 with a 95% confidence interval (CI) of 0.37–1.04. The estimate of ERR/Gy, obtained accounting for the uncertainty in estimates of individual doses of liquidators, was 0.64 at 95% CI (0.33–0.98). This estimate bias is not significant, since it is within 95% CI for both ERR/Gy estimates, the statistical range of which is of the order of magnitude of the estimates themselves.
Conclusions: Considering the uncertainty of individual dose estimates in the cohort of Russian liquidators, the estimate of the excess relative rate per dose unit (ERR/Gy) for the incidence of solid cancer does not statistically significantly differ from the estimate obtained directly from the doses registered in the NRER database. The bias in the estimate of the radiation risk coefficient observed, due to the dose uncertainty introduced into the calculation, is due to the statistical properties of the traditional radiation risk models used for radiation epidemiology. The results obtained confirm the high stability and validity of the radiation risk assessments obtained earlier from the doses registered in the NRER for the Russian cohort of Chernobyl liquidators. Further research will allow generalization of the developed method for assessing radiation risks, accounting for the uncertainty of dose estimates, based on the observed likelihood function, to other types of radiation epidemiological risk studies, including case-control and case-cohort studies.
Keywords: radiation risk, incidence, solid cancer, linear non-threshold risk model, liquidators of the accident at the Chernobyl nuclear power plant, external dose, dose uncertainty, bias in the estimate of radiation risk
For citation: Ivanov VK, Chekin SYu, Maksioutov MA, Gorski AI, Karpenko SV, Tumanov KA, Kashcheev VV, Korelo AM, Kochergina EV. Effect of Dose Uncertainty on the Assessment of Radiation Risks of Solid Cancer Incidence in a Cohort of Russian Participants in the Elimination of the Consequences of the Accident at the Chernobyl NPP. Medical Radiology and Radiation Safety. 2022;67(4):36-41. DOI: 10.33266/1024-6177-2022-67-4-36-41
References
1. Публикация 103 Международной комиссии по радиационной защите (МКРЗ) / Пер. с англ. Киселёва М.Ф., Шандалы Н.К. М.: Изд. ООО ПКФ «Алана», 2009. 312 с. [Электронный ресурс]. URL: http://www.icrp.org/docs/P103_Russian.pdf (дата обращения 15.01.2022).
2. Preston D.L., Ron E., Tokuoka S., Funamoto S., Nishi N., Soda M., Mabuchi K., Kodama K. Solid Cancer Incidence in Atomic Bomb Survivors: 1958–1998 // Radiat. Res. 2007. V.168, No. 1. P. 1–64.
3. Ozasa K., Shimizu Y., Suyama A., Kasagi F., Soda M., Grant E.J., Sakata R., Sugiyama H., Kodama K. Studies of the Mortality of Atomic Bomb Survivors, Report 14, 1950–2003: an Overview of Cancer and Noncancer Diseases // Radiat. Res. 2012. V.177, No. 3. P. 229–243.
4. Grant E.J., Brenner A., Sugiyama H., Sakata R., Sadakane A., Utada M., Cahoon E.K., Milder C.M., Soda M., Cullings H.M., Preston D.L., Mabuchi K., Ozasa K. Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958–2009 // Radiat. Res. 2017. V.187, No.5. P. 513–537.
5. Нормы радиационной безопасности (НРБ-99/2009). Санитарные правила и нормативы. СанПин 2.6.1.2523-09. М.: Федеральный центр гигиены и эпидемиологии Роспотребнадзора, 2009. 100 с.
6. Ivanov V.K., Tsyb A.F., Gorsky A.I., Maksyutov M.A., Rastopchin E.M., Konogorov A.P., Korelo A.M., Biryukov A.P., Matyash V.A. Leukaemia and Thyroid Cancer in Emergency Workers of the Chernobyl Accident: Estimation of Radiation Risks (1986–1995) // Radiat. Environ. Biophys. 1997. V.36, No. 1. P. 9–16.
7. Ivanov V.K., Rastopchin E.M., Gorsky A.I., Ryvkin V.B. Cancer Incidence among Liquidators of the Chernobyl Accident: Solid Tumors, 1986– 1995 // Health Phys. 1998. V.74, No. 3. P. 309–315.
8. Ivanov V.K., Kashcheev V.V., Chekin S.Y., Maksioutov M.A., Tumanov K.A, Vlasov O.K., Shchukina N.V., Tsyb A.F. Radiation-Epidemiological Studies of Thyroid Cancer Incidence in Russia after the Chernobyl Accident (Estimation of Radiation Risks, 1991–2008 Follow-up Period) // Radiat. Prot. Dosimetry. 2012. V.151, No. 3. P. 489–499.
9. Kashcheev V.V., ChekinS.Yu., Maksiutov M.A., Tumanov K.A., Kochergina E.V., Kashcheeva P.V., Shchukina N.V. Incidence and Mortality of Solid Cancer among Emergency Workers of the Chernobyl Accident: Assessment of Radiation Risks for the Follow-up of 1992–2009 // Radiat. Eviron. Biophys. 2015. V.54, No. 1. P. 13–23.
10. Кащеев В.В., Чекин С.Ю., Карпенко С.В., Максютов М.А., Туманов К.А., Кочергина Е.В., Глебова С.Е., Иванов С.А., Каприн А.Д. Оценка радиационных рисков злокачественных новообразований среди российских участников ликвидации последствий аварии на Чернобыльской АЭС // Радиация и риск. 2021. Т.30, № 1. С. 58–77.
11. Медицинские радиологические последствия Чернобыля: прогноз и фактические данные спустя 30 лет / Под ред. чл.-корр. РАН Иванова В.К., чл.-корр. РАН Каприна А.Д. М.: ГЕОС, 2015. 450 с.
12. Питкевич В.А., Иванов В.К., Цыб А.Ф., Максютов М.А., Матяш В.А., Щукина Н.В. Дозиметрические данные Российского государственного медико-дозиметрического регистра для ликвидаторов // Радиация и риск. 1995. № 2. С. 3–44.
13. Gillies M., Haylock R. The Cancer Mortality and Incidence Experience of Workers at British Nuclear Fuels plc, 1946–2005 // J. Radiol. Prot. 2014. V.34, № 3. P. 595–623.
14. United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). Effects of Ionizing Radiation. UNSCEAR 2006 Report to the General Assembly with Scientific Annexes. V. I. New York: United Nations, 2008. 392 p. [Электронный ресурс]. URL: https://www.unscear.org/docs/publications/2006/UNSCEAR_2006_Report_Vol.I.pdf (дата обращения 15.01.2022).
15. United Nations Scientific Committee on the Effects of Atomic Radiation UNSCEAR 2012 Report to the General Assembly, with scientific annexes. Scientific Annexes. New York: United Nations, 2015. 232 p. [Электронный ресурс]. URL: https://www.unscear.org/docs/publications/2012/UNSCEAR_2012_Annex-B.pdf (дата обращения 15.01.2022).
16. Breslow N., Day N. Statistical Methods in Cancer Research. V. II. The Design and Analysis of Cohort Studies. IARC Scientific Publication No. 82. Lyon: IARC, 1987. 406 p.
17. Международная статистическая классификация болезней и проблем, связанных со здоровьем, 10-й пересмотр (МКБ-10). Т. 1. Ч. 1. Женева: ВОЗ, 1995. 698 с.
18. Ivanov V.K., Gorsky A.I., Kashcheev V.V., Maksioutov M.A., Tumanov K.A. Latent Period in Induction of Radiogenic Solid Tumors in the Cohort of Emergency Workers // Radiat. Environ. Biophys. 2009. V.48, № 3. P. 247–252.
19. Stram D.O., Kopecky K.J. Power and Uncertainty Analysis of Epidemiological Studies of Radiation-Related Disease Risk in Which Dose Estimates are Based on a Complex Dosimetry System: Some Observations // Radiat. Res. 2003. V.160, No. 4. P. 408–417.
20. Wu Y., Hoffman F.O., Apostoaei A.I., Kwon D., Thomas B.A., Glass R., Zablotska L.B. Methods to Account for Uncertainties in Exposure Assessment in Studies of Environmental Exposures // Environ. Health. 2019. V.18, No. 1. P. 31. [Электронный ресурс]. URL: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454753/pdf/12940_2019_ Article_468.pdf (дата обращения 15.01.2022).
21. Stayner L., Vrijheid M., Cardis E., Stram D.O., Deltour I., Gilbert S.J., Howe G. A Monte Carlo Maximum Likelihood Method for Estimating Uncertainty Arising from Shared Errors in Exposures in Epidemiological Studies of Nuclear Workers // Radiat. Res. 2007. V.168, No. 3. P. 757– 763.
22. Breslow N.E. Discussion of the Paper by D.R. Cox // J. R. Statist. Soc. B. 1972. No. 34. P. 216–217.
23. Lyn D.Y. On the Breslow Estimator // Lifetime Data Anal. 2007. No. 13. P. 471–480. [Электронный ресурс]. URL: https://www.ncbi. nlm.nih.gov/pmc/articles/PMC6454753/pdf/12940_2019_Article_468.pdf (дата обращения 15.01.2022)
24. Breslow N., Day N. The Analysis of Case-Control Studies. V. I. // Statistical Methods in Cancer Research. IARC Scientific Publication No. 32. Lyon: IARC, 1980. 350 p.
25. Pierce D.A., Vaeth M., Cologne J.B. Allowance for Random Dose Estimation Errors in Atomic Bomb Survivor Studies: a Revision // Radiat. Res. 2008. V.170, No. 1. P. 118–126.
PDF (RUS) Full-text article (in Russian)
Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.
Финансирование. Исследование не имело спонсорской поддержки.
Участие авторов. Cтатья подготовлена с равным участием авторов.
Поступила: 15.03.2022. Принята к публикации: 11.05.2022.
Medical Radiology and Radiation Safety. 2022. Vol. 67. № 4
Transmission of Radiation-Induced Genome Instability
from Irradiated Parents to their Offspring
D.S. Oslina, V.L. Rybkina, T.V. Azizova
Southern Urals Biophysics Institute, Ozyorsk, Chelyabinsk region, Russia
Contact person: Oslina Darja Sergeevna, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. , This email address is being protected from spambots. You need JavaScript enabled to view it.
Abstract
Numerous studies allow to suppose a transmission of radiation-induced genome instability from irradiated parents to their offspring on cell, chromosome and molecular genetic level. This review focuses on transmission of radiation-induced genome instability from irradiated parents to their offspring. Data of genome instability in animal experiments and in offspring of occupationally exposed human or human exposed in a radiation accident, and in offspring of parents exposed to radiotherapy are reviewed. The possible mechanisms of lineage transmission of genome instability are discussed. High dose irradiation can lead to DNA damage, changes in methylation patterns and miRNAs expression in parents and their offspring and result in mutations, chromosome aberration and destabilization of genome. Non-coding RNAs (miRNA, piRNA, nsRNA) are supposed to contribute to transgenerational effects, since they can target genes, change chromatin structure and disregulate gene expression.
Keywords: ionizing radiation, transgenerational effects, genetic effects, epigenetic effects
For citation: Oslina DS, Rybkina VL, Azizova TV. Transmission of Radiation-Induced Genome Instability from Irradiated Parents to their Offspring. Medical Radiology and Radiation Safety. 2022;67(4):10-18. DOI: 10.33266/1024-6177-2022-67-4-10-18
References
1. Morgan WF. Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation? Oncogene. 2003; 22: 7094–7099.
2. Morgan WF, Sowa MB. Non-targeted bystander effects induced by ionizing radiation. Mutation Research. 2007; 616: 159–164.
3. Kovalchuk I, Kovalchuk O. Genome Stability: From Virus to Human Application. Academic Press; 2016. 712 pp.
4. Dugan LC, Bedford JS. Are Chromosomal Instabilities Induced by Exposure of Cultured Normal Human Cells to Low- or High-LET Radiation? Radiat Res. 2003; 159(3): 301–311.
5. Patkin EL, Pavlinova LI, Sofronov GA. Influence of ecotoxicants on mammalian embryogenesis and gametogenesis: epigenetic mechanisms. Interdisciplinary scientific and applied journal "Biosphere". 2013; 5(4): 450–472.
6. Baverstock K. Why do we need a new paradigm in radiobiology? Mutation Research. 2010; 687: 3–6.
7. Little MP, Goodhead DT, Bridges BA, Bouffler SD. Evidence relevant to untargeted and transgenerational effects in the offspring of irradiated parents. Mutation Research. 2013; 753(1): 50–67.
8. Committee on Medical Aspects of Radiation in the Environment (COMARE). Seventh Report. Chilton, National Radiological Protection Board; 2002. Parents occupationally exposed to radiation prior to the conception of their children. A review of the evidence concerning the incidence of cancer in their children.
9. Committee on Medical Aspects of Radiation in the Environment (COMARE). Eighth Report. Chilton, National Radiological Protection Board; 2004. Review of pregnancy outcomes following preconceptional exposure to radiation.
10. Slovinská L, Elbertová A, Mišúrová E. Transmission of genome damage from irradiated male rats to their progeny. Mutation Research. 2004: 559; 29–37.
11. Mughal SK, Myazin AE, Zhavoronkov LP, Mughal SK, Myazin AE, Zhavoronkov LP, Rubanovich AV, Dubrova YE. The dose and dose-rate effects of paternal irradiation on transgenerational instability in mice: a radiotherapy connection. PLoS One. 2012; 7(7): 1−5.
12. Glen CD, Dubrova YE. Exposure to anticancer drugs can result in transgenerational genomic instability in mice. Proc Natl Acad Sci USA. 2012; 109: 2984–2988.
13. Lomaeva MG, Vasil’eva GV, Fomenko LA, Antipova VN, Gaziev AI, Bezlepkin VG. Increased Genomic Instability in Somatic Cells of the Progeny of Female Mice Exposed to Acute X−Radiation in the Preconceptional Period. Rus J Genetics. 2011; 47(10): 1221.
14. Lomaeva МG, Fomenko LA, Vasil’eva GV, Bezlepkin VG. Tissue-specific Changes in the Polymorphism of Simple Repeats in DNA of the Offspring of Different Sex Born from Irradiated Male or Female Mice. Radiation biology. Radioecology. 2016; 56(2): 149–155.
15. Nefedov IY, Nefedova IY, Palyga GF. Actual aspects of the problem of the genetic consequences of mammalian exposure. Radiation biology. Radioecology. 2000; 40(4); 358–372.
16. Abouzeid AHE, Barber RC, Dubrova YE. The effects of maternal irradiation during adulthood on mutation induction and transgenerational instability in mice. Mutation Research. 2012; 732: 21–25.
17. Somers CM. Expanded simple tandem repeat (ESTR) mutation induction in the male germline: lessons learned from lab mice. Mutation Research. 2006; 598: 35–49.
18. Barber RC, Hickenbotham P, Hatch T, Kelly D, Topchiy N, Almeida GM, Jones GD, Johnson GE, Parry JM, Rothkamm K, Dubrova YE. Radiation-induced transgenerational alterations in genome stability and DNA damage. Oncogene. 2006; 25: 7336–7342.
19. Min H, Sung M, Son M, Kawasaki I, Shim YH. Transgenerational effects of proton beam irradiation on Caenorhabditis elegans germline apoptosis. Biochemical and Biophysical Research Communications. 2017; 490(3): 608–615.
20. Parisot F, Bourdineaud JP, Plaire D, Adam-Guillermin C, Alonzo F. DNA alterations and effects on growth and reproduction in Daphnia magna during chronic exposure to gamma radiation over three successive generations. Aquatic Toxicology. 2015; 163: 27–36.
21. Sarapultseva EI, Dubrova YE. The long-term effects of acute exposure to ionising radiation on survival and fertility in Daphnia magna. Environmental Research. 2016; 150: 138–143.
22. Smith RW, Seymour CB, Moccia RD, Mothersill CE. Irradiation of rainbow trout at early life stages results in trans-generational effects including the induction of a bystander effect in non-irradiated fish. Environmental Research. 2016; 145: 26–38.
23. Shimada Atsuko, Shima Akihiro. Transgenerational genomic instability as revealed by a somatic mutation assay using the medaka fish. Mutation Research. 2004; 552: 119–124.
24. Tsyusko O, Glenn T, Yi Y, Joice G, Jones K, Aizawa K, Coughlin D, Zimbrick J, Hinton T. Differential genetic responses to ionizing irradiation in individual families of Japanese medaka. Mutation Research. 2011; 718: 18–23.
25. Hurem S, Gomes T, Brede DA, Lindbo Hansen E, Mutoloki S, Fernandez C, Mothersill C, Salbu B, Kassaye YA, Olsen AK, Oughton D, Aleström P, Lyche JL. Parental gamma irradiation induces reprotoxic effects accompanied by genomic instability in zebrafish (Danio rerio) embryos. Environmental Research. 2017; 159: 564–578.
26. Hurem S, Martín LM, Lindeman L, Brede DA, Salbu B, Lyche JL, Aleström P, Kamstra JH. Parental exposure to gamma radiation causes progressively altered transcriptomes linked to adverse effects in zebrafish offspring. Environmental Pollution. 2018; 234: 855–863.
27. Gardner MJ, Snee MP, Hall AJ, Powell CA, Downes S, Terrell JD. Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria. BMJ. 1990; 300: 423–429.
28. Dubrova YE, Bersimbaev RI, Djansugurova LB, Tankimanova MK, Mamyrbaeva ZZh, Mustonen R, Lindholm C, Hultén M, Salomaa S. Nuclear weapons tests and human germline mutation rate. Science. 2002; 295: 1037.
29. Livshits LA, Malyarchuk SG, Kravchenko SA, Lukyanova EM, Antipkin YG, Arabskaya LP, Matsuka GH, Petit E, Giraudeau F, Gourmelon P, Vergnaud G, Le Guen B. Children of Chernobyl cleanup workers do not show elevated rates of mutations in minisatellite alleles. Radiation Research. 2001; 155: 74–80.
30. Furitsu K, Ryo H, Yeliseeva KG, Thuy le TT, Kawabata H, Krupnova EV, Trusova VD, Rzheutsky VA, Nakajima H, Kartel N, Nomura T. Microsatellite mutations show no increases in the children of the Chernobyl liquidators. Mutation Research. 2005; 581: 69–82.
31. Kiuru A, Auvinen A, Luokkamaki M, Makkonen K, Veidebaum T, Tekkel M, Rahu M, Hakulinen T, Servomaa K, Rytömaa T, Mustonen R. Hereditary minisatellite mutations among the offspring of Estonian Chernobyl cleanup workers. Radiation Research. 2003; 159: 651–655.
32. Kodaira M, Izumi S. Takahashi N, Nakamura N. No evidence of radiation effect on mutation rates at hypervariable minisatellite loci in the germ cells of atomic bomb survivors. Radiation Research. 2004; 162: 350–356.
33. Bezlepkin VG, Kirillova EN, Zakharova ML, Pavlova OS, Lomaeva MG, Fomenko LA, Antipova VN, Gaziev AI. Delayed and Transgenerational Molecular and Genetic Effects of Prolonged Influence of Ionizing Radiation in Nuclear Plant Workers. Radiation biology. Radioecology. 2011; 51(1); 20–32.
34. Rees GS, Trikik MZ, Winther JF, Tawn EJ, Stovall M, Olsen JH, Rechnitzer C, Schrøder H, Guldberg P, Boice JD Jr. A pilot study examining germline minisatellite mutations in the offspring of Danish childhood and adolescent cancer survivors treated with radiotherapy. Int J Radiat Biol. 2006; 82(3): 153–160.
35. Vignard J, Mirey G, Salles B. Ionizing-radiation induced DNA double-strand breaks: A direct and indirect lighting up. Radiotherapy and Oncology. 2013; 108: 362–369.
36. Tawn EJ, Whitehouse CA, Winther JF, Curwen GB, Rees GS, Stovall M, Olsen JH, Guldberg P, Rechnitzer C, Schrøder H, Boice JD Jr. Chromosome analysis in childhood cancer survivors and their offspring – no evidence for radiotherapy-induced persistent genomic instability. Mutation Research. 2005; 583: 198–206.
37. Signorello LB, Mulvihill JJ, Green DM, Munro HM, Stovall M, Weathers RE, Mertens AC, Whitton JA, Robison LL, Boice JD Jr. Stillbirth and neonatal death in relation to radiation exposure before conception: a retrospective cohort study. Lancet. 2010; 376: 624–630.
38. Kuzmina NS, Lapteva NSh, Rubanovich AV. Hypermethylation of gene promoters in peripheral blood leukocytes in humans longterm after radiation exposure. Environmental Research. 2016; 146: 10–17.
39. Suzuki R, Ojima M, Kodama S, Watanabe M. Delayed activation of DNA damage checkpoint and radiation-induced genomic instability. Mutat Res. 2006; 597 (1–2): 73–77.
40. Venkatesan S, Natarajan AT, Hande M. Chromosomal instability—mechanisms and consequences. Mutation Research. 2015; 793: 176–184.
41. Sabatier L, Ricoul M, Pottier G, Murnane JP. The loss of single telomere can result in instability of multiple chromosomes in a human tumor cell line. Mol Cancer Res. 2005; 3: 139–150.
42. Blake GET, Watson ED. Unravelling the complex mechanisms of transgenerational epigenetic inheritance. Current Opinion in Chemical Biology. 2016; 33: 101–107.
43. Molla-Herman A, Matias NR, Huynh JR. Chromatin modifications regulate germ cell development and transgenerational information relay. Current Opinion in Insect Science. 2014; 1: 10–18.
44. Pogribny I, Koturbash I, Tryndyak V, Hudson D, Stevenson SML, Sedelnikova O, Bonner W, Kovalchuk O. Fractionated low-dose radiation exposure leads to accumulation of DNA damage and profound alterations in DNA and histone methylation in the murine thymus. Mol Cancer Res. 2005; 3(10): 553–561.
45. Kovalchuk O, Burke P, Besplug J, Slovack M, Filkowski J, Pogribny I. Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation. Mutation Research. 2004; 548: 75–84.
46. Koturbash I, Boyko A, Rodriguez-Juarez R, McDonald RJ, Tryndyak VP, Kovalchuk I, Pogribny IP, Kovalchuk O. Role of epigenetic effectors in maintenance of the long-term persistent bystander effect in spleen in vivo. Carcinogenesis. 2007; 28(8): 1831–1838.
47. Transgenerational Epigenetics / ed. Tollefsbol T. Academic Press, 2014. 412 pp. http://dx.doi.org/10.1016/B978-0-12-405944-3.00011-8.
48. Niwa O. Indirect mechanisms of radiation induced genomic instability at repeat loci // International Congress Series. 2007; 1299: 135–145.
49. Scully R, Xie A. Double strand break repair functions of histone H2AX. Mutation Research. Fundamental and Molecular Mechanisms of Mutagenesis. 2013; 750 (1–2):5–14.
50. Vasilyev S, Velichevskaya AI, Vishnevskaya TV, Belenko AA, Gribova O, Plaksin MB, Startseva ZhA, Lebedev I. Background Level of γH2AX Foci in Human Cells as a Factor of Individual Radiosensitivity. Radiation biology. Radioecology. 2015; 55(4): 402–410.
51. Merrifield M, Kovalchuk O. Sins of Fathers Through a Scientific Lens: Transgenerational Effects Genome Stability. http://dx.doi.org/10.1016/B978-0-12-803309-8.00034-3
52. Ahmad P, Sana J, Slavik M, Slampa P, Smilek P, Slaby O. MicroRNAs Involvement in Radioresistance of Head and Neck Cancer. Disease Markers. 2017. Article ID 8245345. http://dx.doi.org/10.1155/2017/8245345
53. Ilnytskyy Y, Zemp FJ, Koturbash I, Kovalchuk O. Altered microRNA expression patterns in irradiated hematopoietic tissues suggest a sex-specific protective mechanism. Biochemical and Biophysical Research Communications. 2008; 377: 41–45.
54. Barber RC, Dubrova YE, Gant TW. Radiation-induced transgenerational alterations in MicroRNA expression. Toxicology. 2011; 290: 1–46.
55. Filkowski JN, Ilnytskyy Y, Tamminga J, Koturbash I, Golubov A, Bagnyukova T, Pogribny IP, Kovalchuk O. Hypomethylation and genome instability in the germline of exposed parents and their progeny is associated with altered miRNA expression. Carcinogenesis. 2010; 6: 1110–1115.
56. Aravin AA, Sachidanandam R, Bourc’his D, Schaefer C, Pezic D, Fejes Toth K, Bestor T, Hannon GJ. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell. 2008; 31(6): 785–799.
57. Thomson T, Lin H. The biogenesis and function of PIWI proteins and piRNAs: progress and prospect. Annu Rev Cell Dev Biol. 2009; 25: 355–376.
58. Rechavi O, Houri-Ze’evi L, Anava S, Goh WSS, Kerk SY, Hannon GJ, Hobert O. Starvation-Induced Transgenerational Inheritance of Small RNAs in C. elegans. Cell. 2014; 158: 277–287.
59. Nelson VR Nadeau JH. Transgenerational genetic effects. Epigenomics. 2010; 2(6):797–806.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The study had no sponsorship.
Contribution. Article was prepared with equal participation of the authors.
Article received: 15.03.2022. Accepted for publication: 11.05.2022
Medical Radiology and Radiation Safety. 2022. Vol. 67. № 4
Peculiarities of Human Tumor HeLa Cells Surviving and Giving
a Stable Growth After Acute X-ray Irradiation
D.V. Guryev1, 2, A.A. Tsishnatti1, 3, S.M. Rodneva1, Yu.A. Fedotov1, 2,
D.V. Molodtsova1, T.M. Blokhinа1, 2, E.I. Yashkina1, 2,
A.N. Osipov1, 2
1A.I. Burnasyan Federal Medical Biophysical Center, Moscow, Russia
2N.N. Semenov Federal Research Center for Chemical Physics, Moscow, Russia
3National Research Nuclear University MEPHI, Moscow, Russia
Contact person: D.V. Guryev, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Purpose: The evaluation of the repair efficiency of DNA double-strand breaks (DSB), proliferative activity and the yield of cytogenetic disorders in human tumor HeLa cells which survived and gave stable growth after acute irradiation at a dose of 15 Gy.
Material and methods: HeLa human tumor cell line (cervical carcinoma) was used. Cells were irradiated on an X-ray biological installation RUST-M1 (Russia), equipped with two X-ray emitters, at a dose rate of 0.85 Gy / min, a voltage of 200 kV, a total current of 10 mA, and a 1.5 mm Al filter. To obtain clones of surviving cells (HeLaRR), after acute irradiation at a dose of 15 Gy, cell cultures were incubated under standard CO2 incubator conditions (37 °C, 5 % CO2) for several weeks until well proliferating cells were obtained. Immunocytochemical staining of the foci of the phosphorylated H2AX protein (γH2AX) was used to quantitatively evaluate the residual foci of DNA DSB repair. The micronuclei number was assessed in cytochalasin-B cytokinesis-blocked binucleated cells stained with acridine orange with luminescence microscopy. The doubling time of the cell population was analyzed by the cell growth curves obtained by daily cell counting for five days. The cell cycle stages distribution was assessed by flow cytometry using the propidium iodide dye. All quantitative indicators of the studies were processed using the Student’s t-test for independent samples and the Kolmogorov – Smirnov test.
Results: It was revealed that acute irradiation at a high dose leads to the selection of cells with a higher reparative capacity which is confirmed by the low yield of residual foci of DNA DSB repair and MN after testing irradiation at doses of 5 and 10 Gy. A significant decrease in the proliferative activity of cells that survived after acute X-ray irradiation at a dose of 15 Gy was revealed. The doubling time of the population of unirradiated cells at the stage of exponential growth was ~18 hours while for cells that survived after irradiation at a dose of 15 Gy ~42 hours. A change in the cell cycle phases distribution was observed.
Conclusion: Thus, acute irradiation at a high dose leads to the selection of cells with a higher reparative capacity which is confirmed by the low yield of residual γH2AX foci and MN after testing irradiation at doses of 5 and 10 Gy. The decrease in proliferative activity was accompanied by a change in the cell cycle phases distribution.
Keywords: HeLa, γH2AX, micronuclei, proliferation, residual foci, DNA double-strand breaks, Х-ray
For citation: Guryev DV, Tsishnatti AA, Rodneva SM, Fedotov YuA, Molodtsova DV, Blokhinа TM, Yashkina E.I., Osipov AN. Peculiarities of Human Tumor HeLa Cells Surviving and Giving a Stable Growth After Acute X-ray Irradiation. Medical Radiology and Radiation Safety. 2022;67(4):5–9. (In Russian). DOI:10.33266/1024-6177-2022-67-4-5-9
References
1. Dean M., Fojo T., Bates S.. Tumour Stem Cells and Drug Resistance. Nat. Rev. Cancer. 2005;5;4:275-284.
2. Alhaddad L., Pustovalova M., Blokhina T., Chuprov-Netochin R., Osipov A.N., Leonov S. IR-Surviving NSCLC Cells Exhibit Different Patterns of Molecular and Cellular Reactions Relating to the Multifraction Irradiation Regimen and p53-Family Proteins Expression. Cancers. 2021;13;11:2669.
3. Pustovalova M., Alhaddad L., Smetanina N., Chigasova A., Blokhina T., Chuprov-Netochin R., et al. The p53–53BP1-Related Survival of A549 and H1299 Human Lung Cancer Cells after Multifractionated Radiotherapy Demonstrated Different Response to Additional Acute X-ray Exposure. International Journal of Molecular Sciences. 2020;21;9:3342.
4. Almendro V., Marusyk A., Polyak K. Cellular Heterogeneity and Molecular Evolution in Cancer. Annu. Rev. Pathol. 2013;8:277-302.
5. De Sousa E.M.F., Vermeulen L., Fessler E., Medema J.P. Cancer Heterogeneity-a Multifaceted View. EMBO Rep. 2013;14;8:686-695.
6. Butof R., Dubrovska A., Baumann M.. Clinical Perspectives of Cancer Stem Cell Research in Radiation Oncology. Radiother Oncol. 2013;108;3:388-396.
7. Peitzsch C., Kurth I., Kunz-Schughart L., Baumann M., Dubrovska A.. Discovery of the Cancer Stem Cell Related Determinants of Radioresistance. Radiother Oncol. 2013;108;3:378-387.
8. Krause M., Dubrovska A., Linge A., Baumann M. Cancer Stem Cells: Radioresistance, Prediction of Radiotherapy Outcome and Specific Targets for Combined Treatments. Adv. Drug. Deliv. Rev. 2017;109:63-73.
9. Pustovalova M., Alhaddad L., Blokhina T., Smetanina N., Chigasova A., Chuprov-Netochin R., et al. The CD44high Subpopulation of Multifraction Irradiation-Surviving NSCLC Cells Exhibits Partial EMT-Program Activation and DNA Damage Response Depending on Their p53 Status. International Journal of Molecular Sciences. 2021;22;5:2369.
10. Peitzsch C., Tyutyunnykova A., Pantel K., Dubrovska A. Cancer Stem Cells: The Root of Tumor Recurrence and Metastases. Semin Cancer Biol. 2017;44:10-24.
11. International Atomic Energy Agency. Cytogenetic Analysis for Radiation Dose Assessment: a Manual. Vienna, International Atomic Energy Agency, 2001. 127 p.
12. Siddiqui M.S., Francois M., Fenech M.F., Leifert W.R. Persistent GammaH2AX: A Promising Molecular Marker of DNA Damage and Aging. Mutat. Res. Rev. Mutat. Res. 2015;766:1-19.
13. Sorokin M., Kholodenko R., Grekhova A., Suntsova M., Pustovalova M., Vorobyeva N., et al. Acquired Resistance to Tyrosine Kinase Inhibitors May be Linked with the Decreased Sensitivity to X-Ray Irradiation. Oncotarget. 2017;9;4:5111-5124.
14. Babayan N., Vorobyeva N., Grigoryan B., Grekhova A., Pustovalova M., Rodneva S., et al. Low Repair Capacity of DNA Double-Strand Breaks Induced by Laser-Driven Ultrashort Electron Beams in Cancer Cells. International Journal of Molecular Sciences. 2020;21;24:9488.
15. Banáth J.P., Klokov D., MacPhail S.H., Banuelos C.A., Olive P.L. Residual γH2AX Foci as an Indication of Lethal DNA Lesions. BMC Cancer. 2010;10;1.
16. Raavi V., Perumal V., Paul S.F.D. Potential Application of γ-H2AX as a Biodosimetry Tool for Radiation Triage. Mutation Research/Reviews in Mutation Research. 2021;787:108350.
17. Vaurijoux A., Voisin P., Freneau A., Barquinero J.F., Gruel G. Transmission of Persistent Ionizing Radiation-Induced Foci Through Cell Division in Human Primary Cells. Mutat Res. 2017;797-799:15-25.
18. Akudugu J.M., Theron T., Serafin A.M., Bohm L. Influence of DNA Double-Strand Break Rejoining on Clonogenic Survival and Micronucleus Yield in Human Cell Lines. Int. J. Radiat. Biol. 2004;80;2:93-104.
19. Akudugu J.M., Bohm L. Micronuclei and Apoptosis in Glioma and Neuroblastoma Cell Lines and Role of Other Lesions in the Reconstruction of Cellular Radiosensitivity. Radiat Environ Biophys. 2001;40;4:295-300.
20. Liu C., Nie J., Wang R., Mao W. The Cell Cycle G2/M Block Is an Indicator of Cellular Radiosensitivity. Dose-Response. 2019;17;4:155932581989100.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. All authors made the same contribution to the conception, design, conduction, date analysis of the investigation and the creation of the text of the article.
Financing. The work was conducted by the research state task «Development of approaches to reduce the radioresistance of tumor stem cells» (АААА-А19-119122000097-6).
Contribution. Article was prepared with equal participation of the authors.
Article received: 17.01.2022. Accepted for publication: 15.03.2022.
Medical Radiology and Radiation Safety. 2022. Vol. 67. № 4
Hygienic Aspects of Special Assessment of Working Conditions with Ionizing Radiation Sources
N.L. Proskuryakova, A.V. Simakov, Yu.V. Abramov
A.I. Burnasyan Federal Medical Biophysical Center, Moscow, Russia.
Contact person: Proskuryakova Natalia Leonidovna, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Purpose: Substantiation of hygienic approaches to assessing the working conditions of personnel when working with sources of ionizing radiation.
Material and methods: The article considers one of the most important components of the complex of measures to solve the problem of ensuring radiation safety – conducting a special assessment of the working conditions (SAWC) of workers exposed to radiation from ionizing radiation sources (IRS) in the course of production activities. The issues of assessing occupational risks for workers in working conditions when working with IRS at nuclear energy use facilities are touched upon.
Results: At present, the Procedure for conducting the SAWC is determined by Federal Law No. 426-FZ dated December 28, 2013 «On special assessment of working Conditions» and the Methodology for conducting a special assessment of working conditions (approved by the order of the Ministry of Labor of the Russian Federation dated November 14, 2016, No. 642n). The established procedure for carrying out the SAWC is based on the hygienic criteria for the classification of working conditions defined by the Guidelines P 2.2.2006-05 and P 2.6.5.07–2019. Working conditions when working with ionizing radiation sources, unlike the effects of other harmful production factors, are characterized by the presence of harmful production factors that do not exceed hygienic standards, and the degree of harmfulness of working conditions is determined not so much by the severity of threshold deterministic effects in workers when irradiating individual organs, but primarily by an increase in the risk of stochastic non-threshold effects.
Conclusion: When conducting the SAWC of workers exposed to radiation from ionizing radiation sources in the course of production activities, it is necessary to take into account the following distinctive characteristics of the effects of ionizing radiation:
– in contrast to the principles of classification of working conditions set out in P 2.2.755-99 and Federal Law No. 426-FZ, when working with IRS, harmful working conditions are characterized by the presence of production factors that do not exceed hygienic standards;
– when working with ionizing radiation sources, the degree of harmfulness of working conditions is determined not only by the severity of the manifestation of threshold deterministic effects in workers, but mainly by an increase in the risk of stochastic threshold-free effects;
– the correct conduct of the SAWC and assessment of working conditions according to the indicators of harmfulness and danger when working with IRS are a prerequisite for the quantitative assessment of the occupational risk of employees of the nuclear energy use facilities.
Keywords: working environment, special assessment, hygiene criteria, radiation safety, ionizing radition, occupational risks
For citation: Proskuryakova NL, Simakov AV, Abramov YuV. Hygienic Aspects of Special Assessment of Working Conditions with Ionizing Radiation Sources. Medical Radiology and Radiation Safety. 2022;67(4):19-23. DOI: 10.33266/1024-6177-2022-67-4-19-23
References
1. Manual R 2.2.2006-05. Guidelines for the hygienic assessment of factors of the working environment and the labor process. Criteria and classification of working conditions (In Russian).
2. Manual R 2.2/2.6.1.1195–03. Hygienic criteria for assessing working conditions and classification of workplaces when working with ionizing radiation sources (In Russian).
3. Manual R 2.6.5.07-2019. Hygienic criteria for special assessment and classification of working conditions when working with ionizing radiation sources (In Russian).
4. SanPiN 2.6.1.2523-09. Radiation Safety Standards (NRB-99/2009) M. 2009 (In Russian)).
5. Simakov A.V., Kochetkov O.A., Abramov Yu.V. Scientific substantiation of hygienic criteria of working environment assessment regarding ionizing radiation sources interaction / in Proceedings Int. Conf. “Current issues of radiation hygiene», 2004, St.-Petersburg, p. 36-38.
6. Simakov A.V., Abramov Yu.V. Assessment and classification of working environment regarding ionizing radiation sources interaction/ in Anniversary Proceedings « 50 years Head CSSES of Federal department «Medbioekstrem».,2004, M., p.164-169;
7. Simakov A.V., Abramov Yu.V. Certification of workplaces regarding ionizing radiation sources interaction. Proceedings Materials of the X Russian Congress of Hygienists and Sanitary Doctors. 2007. book II, p. 1253-1256.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The study had no sponsorship.
Contribution. Article was prepared with equal participation of the authors.
Article received: 18.01.2022. Accepted for publication: 11.05.2022




