mesЭкстремальная биомедицинаExtreme Medicine3033-89643033-8972Centre for Strategic Planning of the Federal Medical and Biological Agency10.47183/mes.2024-26-3-5-14mes-111Research ArticleРАДИОБИОЛОГИЯRADIOBIOLOGYРетроспективная биодозиметрия. Проблема конвертации частоты хромосомных транслокаций в дозу на органыRetrospective biodosimetry: Conversion of frequency of chromosomal translocations into organ doseshttps://orcid.org/0000-0002-4958-3214ТолстыхЕ. И.TolstykhE. I.

Толстых Евгения Игоревна, д-р биол. наук 

Челябинск

Chelyabinsk

evgenia.tolstykh@yandex.ruhttps://orcid.org/0000-0003-4394-2228АхмадуллинаЮ. Р.AkhmadullinaY. R.

Ахмадуллина Юлия Рафисовна, канд. биол. наук

Челябинск

Chelyabinsk

Akhmadullina@urcrm.ruhttps://orcid.org/0000-0002-1457-4916ШарагинП. А.SharaginP. A.Шарагин Павел Алексеевич

Челябинск

Chelyabinsk

sharagin@urcrm.ruhttps://orcid.org/0000-0003-4464-0889ШишкинаЕ. А.ShishkinaE. A.

Шишкина Елена Анатольевна, д-р. биол. наук

Челябинск

Chelyabinsk

lena@urcrm.ruhttps://orcid.org/0000-0003-2583-5808АклеевА. В.AkleyevA. V.

Аклеев Александр Васильевич, д-р мед. наук, профессор

Челябинск

Chelyabinsk

akleyev@urcrm.ruУральский научно-практический центр радиационной медицины Федерального медико-биологического агентстваРоссияUrals Research Center for Radiation MedicineRussian FederationУральский научно-практический центр радиационной медицины Федерального медико-биологического агентства; Челябинский государственный университетРоссияUrals Research Center for Radiation Medicine; Chelyabinsk State UniversityRussian Federation202425102024263514Copyright © Толстых Е.И., Ахмадуллина Ю.Р., Шарагин П.А., Шишкина Е.А., Аклеев А.В., 20242024Толстых Е.И., Ахмадуллина Ю.Р., Шарагин П.А., Шишкина Е.А., Аклеев А.В.Tolstykh E.I., Akhmadullina Y.R., Sharagin P.A., Shishkina E.A., Akleyev A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.extrememedicine.ru/jour/article/view/111Введение

Введение. Одним из методов ретроспективной биодозиметрии является учет стабильных хромосомных аберраций (транслокаций) в Т-лимфоцитах периферической крови человека с использованием метода FISH (fluorescence in situ hybridization). В случае равномерно внешнего или внутреннего облучения интерпретация данных FISH не вызывает проблем: доза на Т-лимфоциты, определяющая частоту транслокаций, трактуется как доза на другие органы и ткани. В случае неравномерного внутреннего облучения, когда дозы облучения органов различаются на порядок величины, переход от частоты транслокаций к оценкам дозы требует особых подходов.

Цель

Цель. Рассмотреть основные параметры, которые необходимы для ретроспективной оценки доз с использованием метода FISH в случае внутреннего неравномерного и пролонгированного β-облучения.

Обсуждение

Обсуждение. В аналитическом обзоре были проанализированы проблемы, связанные с определением следующих параметров.

Были проанализированы особенности накопления дозы в различных популяциях Т-клеток при длительном внутреннем неравномерном облучении (на примере 90Sr), а также применимость модельного подхода к оценке накопленных доз. В работе обсуждаются неопределенности дозовых оценок и дальнейшие направления исследований в рамках ретроспективной биодозиметрии.

Introduction

Introduction. One of the techniques used in retrospective biodosimetry according to the fluorescence in situ hybridization (FISH) method involves the estimation of stable chromosome aberrations (translocations) in human peripheral blood T-lymphocytes. In the case of uniform external and internal exposure, the interpretation of FISH data does not pose any problem, since the dose to T-lymphocytes that effects the translocation frequency can be simply interpreted as the dose to other organs and tissues. However, when the internal exposure is non-uniform and the doses to the organs differ by an order of magnitude, conversion from frequency of translocation to dose estimates becomes a complicated task.

Objective

Objective. To review the main parameters necessary for the retrospective assessment of doses using the FISH method in the case of internal uneven and prolonged β-irradiation.

Findings

Findings. The present analytical review considers problems associated with determining the following parameters: (1) Frequency of radiation-induced and background translocations; (2) Conversion factors from the frequency of radiation-induced translocations to the dose to T-lymphocytes (α); (3) Conversion factors from the dose to T-lymphocytes (cytogenetic dose) to the dose to critical organs and tissues (Borg ), which depend on age at the time of exposure. General approaches and estimates of (α) based on the construction of in vivo and in vitro calibration curves for external and internal exposure were analyzed. The dose-accumulation features in different T-cell populations from prolonged internal non-uniform exposure (using 90Sr as an example) were considered in terms of the applicability of the model approach to assessing accumulated doses. Uncertainties of dose estimates in retrospective biodosimetry are discussed and further research directions proposed.

Conclusions

Conclusions. In the case of non-uniform internal exposure with a low dose rate, converting translocation frequency to dose estimates becomes a complex task. The α and Borg conversion coefficients, which are derived from independent data sets, can be based on various approaches, including modelling. Currently, approaches to assessing their uncertainties, as well as the uncertainties of the dose obtained using the FISH method, remain undeveloped. Therefore, these coefficients require further studies.

хромосомные аберрациитранслокациициркулирующие Т-лимфоцитыбиодозиметриявнутреннее неравномерное облучениеchromosomal aberrationstranslocationscirculating T-lymphocytesbiodosimetryinternal non-uniform internal exposureРабота выполнена при финансовой поддержке ФМБА России, номер государственного учета НИР 22040400135-0. Авторы выражают благодарность специалистам Уральского НП Центра радиационной медицины В.А. Кривощапову и С.Б. Епифановой за техническую помощь в работе.The work was carried out with the financial support of the Federal Medical and Biolo. The authors express their gratitude to Viktor A. Krivoshchapov and Svetlana B. Epifanova, specialists of the Urals Research Center for Radiation Medicine, for technical assistance.ReferencesIAEA, International Atomic Energy Agency. Cytogenetic dosimetry: applications in preparedness for and response to radiation emergencies. EPR-Biodosimetry. IAEA, Vienna, Austria. 2011.IAEA, International Atomic Energy Agency. Cytogenetic dosimetry: applications in preparedness for and response to radiation emergencies. EPR-Biodosimetry. IAEA, Vienna, Austria. 2011.Giussani A, Lopez MA, Romm H, Testa A, Ainsbury EA, Degteva M, et al. Eurados review of retrospective dosimetry techniques for internal exposures to ionising radiation and their applications. Radiat Environ Biophys. 2020;59(3):57–387. https://doi.org/10.1007/s00411-020-00845-yGiussani A, Lopez MA, Romm H, Testa A, Ainsbury EA, Degteva M, et al. Eurados review of retrospective dosimetry techniques for internal exposures to ionising radiation and their applications. Radiat Environ Biophys. 2020;59(3):57–387. https://doi.org/10.1007/s00411-020-00845-yNakayama R, Abe Y, Goh Swee Ting V, Nakayama R, Takebayashi N, Nakata A, A Riyoshi K et al. Cytogenetic Biodosimetry in Radiation Emergency Medicine: 4. Overview of Cytogenetic Biodosimetry. Radiation Environment and Medicine. 2022;11(2):91–103. https://doi.org/10.51083/radiatenvironmed.11.2_91Nakayama R, Abe Y, Goh Swee Ting V, Nakayama R, Takebayashi N, Nakata A, A Riyoshi K et al. Cytogenetic Biodosimetry in Radiation Emergency Medicine: 4. Overview of Cytogenetic Biodosimetry. Radiation Environment and Medicine. 2022;11(2):91–103. https://doi.org/10.51083/radiatenvironmed.11.2_91Tolstykh EI, Degteva MO, Vozilova AV, Anspaugh LR. Local bonemarrow exposure: how to interpret the data on stable chromosome aberrations in circulating lymphocytes? (some comments on the use of FISH method for dose reconstruction for Techa riverside Residents). Radiat Environ Biophys. 2017;56(4):389–403. https://doi.org/10.1007/s00411-017-0712-7Tolstykh EI, Degteva MO, Vozilova AV, Anspaugh LR. Local bonemarrow exposure: how to interpret the data on stable chromosome aberrations in circulating lymphocytes? (some comments on the use of FISH method for dose reconstruction for Techa riverside Residents). Radiat Environ Biophys. 2017;56(4):389–403. https://doi.org/10.1007/s00411-017-0712-7Tolstykh EI, Degteva MO, Vozilova AV, Akleyev AV. Interpretation of FISH Results in the Case of Nonuniform Internal Radiation Exposure of Human Body with the Use of Model Approach.Tolstykh EI, Degteva MO, Vozilova AV, Akleyev AV. Interpretation of FISH Results in the Case of Nonuniform Internal Radiation Exposure of Human Body with the Use of Model Approach.Russian Journal of Genetics. 2019;55(10):1227–33 https://doi.org/10.1134/S1022795419100132Russian Journal of Genetics. 2019;55(10):1227–33 https://doi.org/10.1134/S1022795419100132Tolstykh EI, Vozilova AV, Akleyev AV, Zalyapin VI. Model of agedependent dynamics and biokinetics of T-cells as natural biodosimeters. Radiat Environ Biophys. 2024 Aug;63(3):405–21. https://doi.org/10.1007/s00411-024-01072-5Tolstykh EI, Vozilova AV, Akleyev AV, Zalyapin VI. Model of agedependent dynamics and biokinetics of T-cells as natural biodosimeters. Radiat Environ Biophys. 2024 Aug;63(3):405–21. https://doi.org/10.1007/s00411-024-01072-5Radiological protection — Performance criteria for laboratories using Fluorescence In Situ Hybridization (FISH) translocation assay for assessment of exposure to ionizing radiation. ISO 20046. 2019.Radiological protection — Performance criteria for laboratories using Fluorescence In Situ Hybridization (FISH) translocation assay for assessment of exposure to ionizing radiation. ISO 20046. 2019.Sigurdson AJ, Ha M, Hauptmann M, Bhatti P, Sram RJ, Beskid O, et al. International study of factors affecting human chromosome translocations. Mutat Res. 2008;652(2):112–21. https://doi.org/10.1016/j.mrgentox.2008.01.005Sigurdson AJ, Ha M, Hauptmann M, Bhatti P, Sram RJ, Beskid O, et al. International study of factors affecting human chromosome translocations. Mutat Res. 2008;652(2):112–21. https://doi.org/10.1016/j.mrgentox.2008.01.005Goh VST, Fujishima Y, Abe Y, Sakai A, Yoshida MA, Ariyoshi K et al. Construction of fluorescence in situ hybridization (FISH) translocation dose-response calibration curve with multiple donor data sets using R, based on ISO 20046:2019 recommendations. Int J Radiat Biol. 2019;95(12):1668–84. https://doi.org/10.1080/09553002.2019.1664788Goh VST, Fujishima Y, Abe Y, Sakai A, Yoshida MA, Ariyoshi K et al. Construction of fluorescence in situ hybridization (FISH) translocation dose-response calibration curve with multiple donor data sets using R, based on ISO 20046:2019 recommendations. Int J Radiat Biol. 2019;95(12):1668–84. https://doi.org/10.1080/09553002.2019.1664788Толстых ЕИ. Переход от частоты хромосомных транслокаций в Т-лимфоцитах к дозе на костный мозг в отдаленные сроки после внутреннего облучения 89,90Sr. Радиационная гигиена. 2024;17(2):53–63. https://doi.org/10.21514/1998-426X-2024-17-2-53-63Tolstykh E. I. Conversion from the frequency of chromosome translocations in T-lymphocytes to the bone marrow dose in the long-term period after internal 89,90Sr exposure. Radiation Hygiene. 2024;17(2):53–63 (In Russ). https://doi.org/10.21514/1998-426X-2024-17-2-53-63Tucker JD, Morgan WF, Awa AA, Bauchinger M, Blakey D, Cornforth MN, et al. PAINT: a proposed nomenclature for structural aberrations detected by whole chromosome painting. Mutat Res. 1995 Jun;347(1):21–4. https://doi.org/10.1016/0165-7992(95)90028-4Tucker JD, Morgan WF, Awa AA, Bauchinger M, Blakey D, Cornforth MN, et al. PAINT: a proposed nomenclature for structural aberrations detected by whole chromosome painting. Mutat Res. 1995 Jun;347(1):21–4. https://doi.org/10.1016/0165-7992(95)90028-4Savage JR, Tucker JD. Nomenclature systems for FISH-painted chromosome aberrations. Mutat Res. 1996 Nov;366(2):153–61. https://doi.org/10.1016/s0165-1110(96)90036-6Savage JR, Tucker JD. Nomenclature systems for FISH-painted chromosome aberrations. Mutat Res. 1996 Nov;366(2):153–61. https://doi.org/10.1016/s0165-1110(96)90036-6Stevens-Kroef M, Simons A, Rack K, Hastings RJ. Cyto-genetic Nomenclature and Reporting. Methods Mol Biol. 2017;1541:303–9. https://doi.org/10.1007/978-1-4939-6703-2_24Stevens-Kroef M, Simons A, Rack K, Hastings RJ. Cyto-genetic Nomenclature and Reporting. Methods Mol Biol. 2017;1541:303–9. https://doi.org/10.1007/978-1-4939-6703-2_24Нугиc ВЮ. FISH-метод: способ цитогенетической ретроспективной оценки дозы (обзор). Саратовский научно-медицинский журнал. 2016;12(4):671–8.Nugis VYu. FISH-method: technique of cytogenetic retrospective dose evaluation (review). Saratov Journal of Medical Scientific Research.2016;12(4):671–8 (In Russ.). EDN: YPYFKVFomina J, Darroudi F, Natarajan AT. Accurate detection of true incomplete exchanges in human lymphocytes exposed to neutron radiation using chromosome painting in combination with a telomeric PNA probe. Int J Radiat Biol. 2001;77(12):1175–83. https://doi.org/10.1080/09553000110083951Fomina J, Darroudi F, Natarajan AT. Accurate detection of true incomplete exchanges in human lymphocytes exposed to neutron radiation using chromosome painting in combination with a telomeric PNA probe. Int J Radiat Biol. 2001;77(12):1175–83. https://doi.org/10.1080/09553000110083951Vozilova AV, Krivoshchapova YV. Investigation of the Frequency of Inversions and Complex Translocations in T-Lymphocytes in Exposed Residents of the Southern Urals. Biology Bulletin. 2023;(50):2979–85. https://doi.org/10.1134/s1062359023110237Vozilova AV, Krivoshchapova YV. Investigation of the Frequency of Inversions and Complex Translocations in T-Lymphocytes in Exposed Residents of the Southern Urals. Biology Bulletin. 2023;(50):2979–85. https://doi.org/10.1134/s1062359023110237Pouzoulet F, Roch-Lefèvre S, Giraudet AL, Vaurijoux A, Voisin P, Buard V et al. Monitoring translocations by M-FISH and threecolor FISH painting techniques: a study of two radiotherapy patients. J Radiat Res. 2007;48(5):425–34. https://doi.org/10.1269/jrr.07013Pouzoulet F, Roch-Lefèvre S, Giraudet AL, Vaurijoux A, Voisin P, Buard V et al. Monitoring translocations by M-FISH and threecolor FISH painting techniques: a study of two radiotherapy patients. J Radiat Res. 2007;48(5):425–34. https://doi.org/10.1269/jrr.07013Сотник НВ, Азизова ТВ, Жунтова ГВ. Биоиндикация внутреннего облучения при аварийном поступлении радионуклидов. Медицина экстремальных ситуаций. 2019;21(4):540–7.Sotnik NV, Azizova TV, Zhuntova GV. Bioindication of internal radiation exposure following accidental radionuclide intake. Extreme Medicine. 2019;21(4):540–7 (In Russ.). EDN: YZWAFIHada M, Wu H, Cucinotta FA. mBAND analysis for high- and low-LET radiation-induced chromosome aberrations: a review. Mutat Res. 2011;711(1–2):187–92. https://doi.org/10.1016/j.mrfmmm.2010.12.018Hada M, Wu H, Cucinotta FA. mBAND analysis for high- and low-LET radiation-induced chromosome aberrations: a review. Mutat Res. 2011;711(1–2):187–92. https://doi.org/10.1016/j.mrfmmm.2010.12.018Нугис ВЮ, Снигирева ГП, Ломоносова ЕЕ, Козлова МГ, Никитина ВА. Трехцветный FISH-метод: кривые доза-эффект для транслокаций в культурах лимфоцитов периферической крови после гамма-облучения in vitro. Медицинская радиология и радиационная безопасность. 2021;5:12–20. https://doi.org/10.12737/1024-6177-2020-65-5-12-20Nugis VY, Snigiryova GP, Lomonosova EE, Kozlova MG, Nikitina VA. Three-Color FISH Method: Dose-Effect Curves for Translocations in Peripheral Blood Lymphocyte Cultures after Gamma-Irradiation In Vitro. Medical Radiology and radiation safety. 2021;5:12–20 (In Russ.). https://doi.org/10.12737/1024-6177-2020-65-5-12-20Lea DE, Catcheside DG. The mechanism of the induction by radiation of chromosome aberrations in Tradescantia. Journal of Genetics. 1942; 44(2):216–45. https://doi.org/10.1007/BF02982830Lea DE, Catcheside DG. The mechanism of the induction by radiation of chromosome aberrations in Tradescantia. Journal of Genetics. 1942; 44(2):216–45. https://doi.org/10.1007/BF02982830Bauchinger M, Schmid E, Dresp J. Calculation of the dose-rate dependence of the decentric yield after Co gamma-irradiation of human lymphocytes. Int J Radiat Biol Relat Stud Phys Chem Med. 1979;35(3):229–33. https://doi.org/10.1080/09553007914550261Bauchinger M, Schmid E, Dresp J. Calculation of the dose-rate dependence of the decentric yield after Co gamma-irradiation of human lymphocytes. Int J Radiat Biol Relat Stud Phys Chem Med. 1979;35(3):229–33. https://doi.org/10.1080/09553007914550261Bauchinger M, Schmid E, Zitzelsberger H, Braselmann H, Nahrstedt U. Radiation-induced chromosome aberrations analysed by two-colour fluorescence in situ hybridization with composite whole chromosome-specific DNA probes and a pancentromeric DNA probe. Int J Radiat Biol. 1993;64(2):79–184. https://doi.org/10.1080/09553009314551271Bauchinger M, Schmid E, Zitzelsberger H, Braselmann H, Nahrstedt U. Radiation-induced chromosome aberrations analysed by two-colour fluorescence in situ hybridization with composite whole chromosome-specific DNA probes and a pancentromeric DNA probe. Int J Radiat Biol. 1993;64(2):79–184. https://doi.org/10.1080/09553009314551271Fernández JL, Campos A, Goyanes V, Losada C, Veiras C, Edwards AA. X-ray biological dosimetry performed by selective painting of human chromosomes 1 and 2. Int J Radiat Biol. 1995;67(3):295–302. https://doi.org/10.1080/09553009514550351Fernández JL, Campos A, Goyanes V, Losada C, Veiras C, Edwards AA. X-ray biological dosimetry performed by selective painting of human chromosomes 1 and 2. Int J Radiat Biol. 1995;67(3):295–302. https://doi.org/10.1080/09553009514550351Sasaki MS. Advances in the biophysical and molecular bases of radiation cytogenetics. Int J Radiat Biol. 2009;85(1):26–47. https://doi.org/10.1080/09553000802641185Sasaki MS. Advances in the biophysical and molecular bases of radiation cytogenetics. Int J Radiat Biol. 2009;85(1):26–47. https://doi.org/10.1080/09553000802641185 26. Edwards AA, Lindholm C, Darroudi F, Stephan G, Romm H, Barquinero J, et al. Review of translocations detected by FISH for retrospective biological dosimetry applications. Radiat Prot Dosimetry. 2005;113(4):396–402. https://doi.org/10.1093/rpd/nch452Edwards AA, Lindholm C, Darroudi F, Stephan G, Romm H, Barquinero J, et al. Review of translocations detected by FISH for retrospective biological dosimetry applications. Radiat Prot Dosimetry. 2005;113(4):396–402. https://doi.org/10.1093/rpd/nch452Lindholm C, Luomahaara S, Koivistoinen A, Ilus T, Edwards AA, Salomaa S. Comparison of dose-response curves for chromosomal aberrations established by chromosome painting and conventional analysis. Int J Radiat Biol. 1998;74(1):27–34. https://doi.org/10.1080/095530098141690Lindholm C, Luomahaara S, Koivistoinen A, Ilus T, Edwards AA, Salomaa S. Comparison of dose-response curves for chromosomal aberrations established by chromosome painting and conventional analysis. Int J Radiat Biol. 1998;74(1):27–34. https://doi.org/10.1080/095530098141690Barquinero JF, Beinke C, Borràs M, Buraczewska I, Darroudi F, Gregoire E, et al. RENEB biodosimetry intercomparison analyzing translocations by FISH. Int J Radiat Biol. 2017;93(1):30–5. https://doi.org/10.1080/09553002.2016.1222092Barquinero JF, Beinke C, Borràs M, Buraczewska I, Darroudi F, Gregoire E, et al. RENEB biodosimetry intercomparison analyzing translocations by FISH. Int J Radiat Biol. 2017;93(1):30–5. https://doi.org/10.1080/09553002.2016.1222092Rodríguez P, Montoro A, Barquinero JF, Caballín MR, Villaescusa I, Barrios L. Analysis of translocations in stable cells and their implications in retrospective biological dosimetry. Radiat Res. 2004;162(1):31–8. https://doi.org/10.1667/rr3198Rodríguez P, Montoro A, Barquinero JF, Caballín MR, Villaescusa I, Barrios L. Analysis of translocations in stable cells and their implications in retrospective biological dosimetry. Radiat Res. 2004;162(1):31–8. https://doi.org/10.1667/rr3198Jeong SK, Oh SJ, Kang YR, Kim H, Kye YU, Lee SH, et al. Biological dosimetry dose-response curves for residents living near nuclear power plants in South Korea. Sci Prog. 2023;106(3):368504231198935. https://doi.org/10.1177/00368504231198935Jeong SK, Oh SJ, Kang YR, Kim H, Kye YU, Lee SH, et al. Biological dosimetry dose-response curves for residents living near nuclear power plants in South Korea. Sci Prog. 2023;106(3):368504231198935. https://doi.org/10.1177/00368504231198935Sposto R, Stram DO, Awa AA. An estimate of the magnitude of random errors in the DS86 dosimetry from data on chromosome aberrations and severe epilation. Radiat Res. 1991;128(2):157–69. PMID: 1947012Sposto R, Stram DO, Awa AA. An estimate of the magnitude of random errors in the DS86 dosimetry from data on chromosome aberrations and severe epilation. Radiat Res. 1991;128(2):157–69. PMID: 1947012Stram DO, Sposto R, Preston D, Abrahamson S, Honda T, Awa AA. Stable chromosome aberrations among A-bomb survivors: an update. Radiat Res. 1993;136(1):29–36. PMID: 8210335Stram DO, Sposto R, Preston D, Abrahamson S, Honda T, Awa AA. Stable chromosome aberrations among A-bomb survivors: an update. Radiat Res. 1993;136(1):29–36. PMID: 8210335Awa A. Analysis of chromosome aberrations in atomic bomb survivors for dose assessment: studies at the Radiation Effects Research Foundation from 1968 to 1993. Stem Cells. 1997;15 Suppl 2:163–73.https://doi.org/10.1002/stem.5530150724Awa A. Analysis of chromosome aberrations in atomic bomb survivors for dose assessment: studies at the Radiation Effects Research Foundation from 1968 to 1993. Stem Cells. 1997;15 Suppl 2:163–73.https://doi.org/10.1002/stem.5530150724Sasaki MS, Endo S, Ejima Y, et al. Effective dose of A-bomb radiation in Hiroshima and Nagasaki as assessed by chromosomal effectiveness of spectrum energy photons and neutrons. Radiat Environ Biophys. 2006;45(2):79–91. https://doi.org/10.1007/s00411-006-0051-6Sasaki MS, Endo S, Ejima Y, et al. Effective dose of A-bomb radiation in Hiroshima and Nagasaki as assessed by chromosomal effectiveness of spectrum energy photons and neutrons. Radiat Environ Biophys. 2006;45(2):79–91. https://doi.org/10.1007/s00411-006-0051-6Sasaki MS, Endo S, Ejima Y, Saito I, Okamura K, Oka Y, et al. The Association of Radiation Exposure with Stable Chromosome Aberrations in Atomic Bomb Survivors Based on DS02R1 Dosimetry and FISH Methods. Radiat Res. 2023;199(2):170–81. https://doi.org/10.1667/RADE-22-00154.1Sasaki MS, Endo S, Ejima Y, Saito I, Okamura K, Oka Y, et al. The Association of Radiation Exposure with Stable Chromosome Aberrations in Atomic Bomb Survivors Based on DS02R1 Dosimetry and FISH Methods. Radiat Res. 2023;199(2):170–81. https://doi.org/10.1667/RADE-22-00154.1Tawn EJ, Curwen GB, Jonas P, Gillies M, Hodgson L, Cadwell KK. Chromosome Aberrations Determined by FISH in Radiation Workers from the Sellafield Nuclear Facility. Radiat Res. 2015;184(3):296–303.https://doi.org/10.1667/RR14125.1Tawn EJ, Curwen GB, Jonas P, Gillies M, Hodgson L, Cadwell KK. Chromosome Aberrations Determined by FISH in Radiation Workers from the Sellafield Nuclear Facility. Radiat Res. 2015;184(3):296–303.https://doi.org/10.1667/RR14125.1Tolstykh EI, Vozilova AV, Degteva MO, et al. Dependence of the Translocation Frequency in Blood Lymphocytes on the Dose and Age at the Onset of Exposure in Residents of the Techa Riverside Settlements. Radiacionnaya biologiya. Radioekologiya. 2023;63(2):3184–95 (In Russ.). https://doi.org/10.31857/S086980312302011XТолстых ЕИ, Возилова АВ, Дегтева МО, Аклеев АВ. Зависимость частоты транслокаций в лимфоцитах крови от дозы и возраста на начало облучения у жителей прибрежных сел реки Теча. Радиационная биология. Радиоэкология. 2023;63(2):3184–95.Vrisekoop N, den Braber I, de Boer AB, Ruiter AF, Ackermans MT, van der Crabben SN, et al. Sparse production but preferential incorporation of recently produced naive T cells in the human peripheral pool. Proc Natl Acad Sci USA. 2008;105(16):6115–20. https://doi.org/10.1073/pnas.0709713105Vrisekoop N, den Braber I, de Boer AB, Ruiter AF, Ackermans MT, van der Crabben SN, et al. Sparse production but preferential incorporation of recently produced naive T cells in the human peripheral pool. Proc Natl Acad Sci USA. 2008;105(16):6115–20. https://doi.org/10.1073/pnas.0709713105De Boer RJ, Perelson AS. Quantifcation T lymphocyte turnover. J Theor Biol. 2013;(327):45–87. https://doi.org/10.1016/j.jtbi.2012.12.025De Boer RJ, Perelson AS. Quantifcation T lymphocyte turnover. J Theor Biol. 2013;(327):45–87. https://doi.org/10.1016/j.jtbi.2012.12.025De Boer RJ, Tesselaar K, Borghans JAM. Better safe than sorry: Naive T-cell dynamics in healthy ageing. Semin Immunol. 2023;70:101839. https://doi.org/10.1016/j.smim.2023.101839De Boer RJ, Tesselaar K, Borghans JAM. Better safe than sorry: Naive T-cell dynamics in healthy ageing. Semin Immunol. 2023;70:101839. https://doi.org/10.1016/j.smim.2023.101839Yan J, Greer JM, Hull R, O’Sullivan JD, Henderson RD, Read SJ, et al. The effect of ageing on human lymphocyte subsets: comparison of males and females. Immun Ageing. 2010;7:4. https://doi.org/10.1186/1742-4933-7-4Yan J, Greer JM, Hull R, O’Sullivan JD, Henderson RD, Read SJ, et al. The effect of ageing on human lymphocyte subsets: comparison of males and females. Immun Ageing. 2010;7:4. https://doi.org/10.1186/1742-4933-7-4Den Braber I, Mugwagwa T, Vrisekoop N, Westera L, Mögling R, de Boer AB, et al. Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity. 2012;36(2):288–97 https://doi.org/10.1016/j.immuni.2012.02.006Den Braber I, Mugwagwa T, Vrisekoop N, Westera L, Mögling R, de Boer AB, et al. Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity. 2012;36(2):288–97 https://doi.org/10.1016/j.immuni.2012.02.006Steinmann GG, Klaus B, Muller-Hermelink HK. The involution of the ageing human thymic epithelium is independent of puberty. A morphometric study. Scand J Immunol. 1985;(22):563–75. https://doi.org/10.1111/j.1365–3083.1985.tb01916.xSteinmann GG, Klaus B, Muller-Hermelink HK. The involution of the ageing human thymic epithelium is independent of puberty. A morphometric study. Scand J Immunol. 1985;(22):563–75. https://doi.org/10.1111/j.1365–3083.1985.tb01916.xTolstykh EI, Vozilova AV, Degteva MO, et al. Concept of T-cell genus as the basis for the analysis of FISH results after local bone marrow exposure. Biology Bulletin. 2020;47(11):1495– 506. https://doi.org/10.1134/S1062359020110151Tolstykh EI, Vozilova AV, Degteva MO, et al. Concept of T-cell genus as the basis for the analysis of FISH results after local bone marrow exposure. Biology Bulletin. 2020;47(11):1495– 506. https://doi.org/10.1134/S1062359020110151Degteva MO, Tolstykh EI, Shishkina EA, Sharagin PA, Zalyapin VI, Volchkova AY, et al. Stochastic parametric skeletal dosimetry model for humans: General approach and application to active marrow exposure from bone-seeking beta-particle emitters. PLoS One. 2021;16(10):e0257605. https://doi.org/10.1371/journal.pone.0257605Degteva MO, Tolstykh EI, Shishkina EA, Sharagin PA, Zalyapin VI, Volchkova AY, et al. Stochastic parametric skeletal dosimetry model for humans: General approach and application to active marrow exposure from bone-seeking beta-particle emitters. PLoS One. 2021;16(10):e0257605. https://doi.org/10.1371/journal.pone.0257605Shagina NB, Tolstykh EI, Degteva MO, Anspaugh LR, Napier BA. Age and gender specific biokinetic model for strontium in humans. J Radiol Prot. 2015;35(1):87–127. https://doi.org/10.1088/0952-4746/35/1/87Shagina NB, Tolstykh EI, Degteva MO, Anspaugh LR, Napier BA. Age and gender specific biokinetic model for strontium in humans. J Radiol Prot. 2015;35(1):87–127. https://doi.org/10.1088/0952-4746/35/1/87Tolstykh EI, Degteva MO. Estimation of radiation doses on lymphocytes and their progenitors after ingestion of strontium-89,90. Radiation Hygiene. 2022;15(3):82–91 (In Russ.). https://doi.org/10.21514/1998-426X-2022-15-3-82-91Толстых ЕИ, Дегтева МО. Оценка доз облучения лимфоцитов и их предшественников при пероральном поступлении стронция-89,90. Радиационная гигиена. 2022;15(3):82–91. https://doi.org/10.21514/1998-426X-2022-15-3-82-91Merkle W. Statistical methods in regression and calibration analysis of chromosome aberration data. Radiat Environ Biophys. 1983;21(3):217–33.Merkle W. Statistical methods in regression and calibration analysis of chromosome aberration data. Radiat Environ Biophys. 1983;21(3):217–33.Austin PC, Hux JE. A brief note on overlapping confidence intervals. J Vasc Surg. 2002;36(1):194–5. https://doi.org/10.1067/mva.2002.125015Austin PC, Hux JE. A brief note on overlapping confidence intervals. J Vasc Surg. 2002;36(1):194–5. https://doi.org/10.1067/mva.2002.125015Hernández A, Endesfelder D, Einbeck J, Puig P, Benadjaoud MA, Higueras M, et al. Biodose Tools: An R Shiny Application for Biological Dosimetry. 2023;99(9):1378–90. https://doi.org/10.1080/09553002.2023.2176564Hernández A, Endesfelder D, Einbeck J, Puig P, Benadjaoud MA, Higueras M, et al. Biodose Tools: An R Shiny Application for Biological Dosimetry. 2023;99(9):1378–90. https://doi.org/10.1080/09553002.2023.2176564Higueras M, Puig P, Ainsbury EA, Vinnikov VA, Rothkamm K. A new Bayesian model applied to cytogenetic partial body irradiation estimation. Radiat Prot Dosimetry. 2016;168(3):330–6. https://doi.org/10.1093/rpd/ncv356Higueras M, Puig P, Ainsbury EA, Vinnikov VA, Rothkamm K. A new Bayesian model applied to cytogenetic partial body irradiation estimation. Radiat Prot Dosimetry. 2016;168(3):330–6. https://doi.org/10.1093/rpd/ncv356Ainsbury EA, Lloyd DC: Dose estimation software for radiation biodosimetry. Health Phys. 2010;98(2):290–5. https://doi.org/10.1097/01.HP.0000346305.84577.b4Ainsbury EA, Lloyd DC: Dose estimation software for radiation biodosimetry. Health Phys. 2010;98(2):290–5. https://doi.org/10.1097/01.HP.0000346305.84577.b4Deperas J, Szluinska M, Deperas-Kaminska M, Edwards A, Lloyd D, Lindholm C, et al. CABAS: a freely available PC program for fitting calibration curves in chromosome aberration dosimetry. Radiat Prot Dosimetry. 2007;124(2):115–23. https://doi.org/10.1093/rpd/ncm137Deperas J, Szluinska M, Deperas-Kaminska M, Edwards A, Lloyd D, Lindholm C, et al. CABAS: a freely available PC program for fitting calibration curves in chromosome aberration dosimetry. Radiat Prot Dosimetry. 2007;124(2):115–23. https://doi.org/10.1093/rpd/ncm137Gnanasekaran TS. Cytogenetic biological dosimetry assays: recent developments and updates. Radiat Oncol J. 2021;39(3):159–66. https://doi.org/10.3857/roj.2021.00339Gnanasekaran TS. Cytogenetic biological dosimetry assays: recent developments and updates. Radiat Oncol J. 2021;39(3):159–66. https://doi.org/10.3857/roj.2021.00339Beinke C, Siebenwirth C, Abend M, Port M. Contribution of Biological and EPR Dosimetry to the Medical Management Support of Acute Radiation Health Effects. Appl Magn Reson. 2022;(53):265–87. https://doi.org/10.1007/s00723-021-01457-5Beinke C, Siebenwirth C, Abend M, Port M. Contribution of Biological and EPR Dosimetry to the Medical Management Support of Acute Radiation Health Effects. Appl Magn Reson. 2022;(53):265–87. https://doi.org/10.1007/s00723-021-01457-5M’Kacher R, Colicchio B, Junker S, El Maalouf E, Heidingsfelder L, Plesch A, et al. High Resolution and Automatable Cytogenetic Biodosimetry Using In Situ Telomere and Centromere Hybridization for the Accurate Detection of DNA Damage: An Overview. Int J Mol Sci. 2023;24(6):5699. https://doi.org/10.3390/ijms24065699M’Kacher R, Colicchio B, Junker S, El Maalouf E, Heidingsfelder L, Plesch A, et al. High Resolution and Automatable Cytogenetic Biodosimetry Using In Situ Telomere and Centromere Hybridization for the Accurate Detection of DNA Damage: An Overview. Int J Mol Sci. 2023;24(6):5699. https://doi.org/10.3390/ijms24065699Herate C, Sabatier L. Retrospective biodosimetry techniques: Focus on cytogenetics assays for individuals exposed to ionizing radiation. Mutat Res Rev Mutat Res. 2020;(783):108287. https://doi.org/10.1016/j.mrrev.2019.108287Herate C, Sabatier L. Retrospective biodosimetry techniques: Focus on cytogenetics assays for individuals exposed to ionizing radiation. Mutat Res Rev Mutat Res. 2020;(783):108287. https://doi.org/10.1016/j.mrrev.2019.108287Degteva MO, Shagina NB, Shishkina EA, Vozilova AV, Volchkova AY, Vorobiova MI, et al. Analysis of EPR and FISH studies of radiation doses in persons who lived in the upper reaches of the Techa River. Radiat Environ Biophys. 2015;54(4):433–44. https://doi.org/10.1007/s00411-015-0611-8Degteva MO, Shagina NB, Shishkina EA, Vozilova AV, Volchkova AY, Vorobiova MI, et al. Analysis of EPR and FISH studies of radiation doses in persons who lived in the upper reaches of the Techa River. Radiat Environ Biophys. 2015;54(4):433–44. https://doi.org/10.1007/s00411-015-0611-8Degteva MO, Shishkina EA, Tolstykh EI, et al. Application of the EPR and FISH Methods to Dose Reconstruction for People Exposed in the Techa River Area. Radiats Biol Radioecol. 2017;57(1):30–41. English, Russian. https://doi.org/10.7868/S0869803117010052Degteva MO, Shishkina EA, Tolstykh EI, et al. Application of the EPR and FISH Methods to Dose Reconstruction for People Exposed in the Techa River Area. Radiats Biol Radioecol. 2017;57(1):30–41. English, Russian. https://doi.org/10.7868/S0869803117010052Degteva MO, Shishkina EA, Tolstykh EI, et al. Application of the EPR and FISH Methods to Dose Reconstruction for People Exposed in the Techa River Area. Radiats Biol Radioecol. 2017;57(1):30–41. English, Russian. https://doi.org/10.7868/S0869803117010052

The authors declare that there are no conflicts of interest present.