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Circulating T-lymphocytes are used as "natural biodosimeters" for estimating radiation doses, since the frequency of chromosomal aberrations induced in them is proportional to the accumulated dose. Moreover, stable chromosomal aberrations (translocations) are detected years and decades after exposure. Internal incorporation of radionuclides often leads to non-uniform exposure, which resulted in difficulties in the application of retrospective biodosimetry using T-lymphocytes. Some properties of T-lymphocytes complicate retrospective biodosimetry in this case: (1) the thymic production of T-cells depends significantly on age, the maximum is observed in early childhood; (2) the "lymphocyte-dosimeter" accumulates changes (translocations) while circulating through the body. The objective of this paper is to describe the technical characteristics of the model of age dynamics and T-cell biokinetics and approaches to assessing the dose to circulating lymphocytes under various exposure scenarios. The model allows to quantify the fractions of T-lymphocytes that were formed before and after exposure. The model takes into account the time fractions that circulating lymphocytes spend in various lymphoid organs. Age-related thymic involution was also considered. The model predicts that after internal exposure to 90 Sr, the doses to T-lymphocytes can differ significantly from the doses to the bone marrow and other tissues. For uniform external γ-exposure, and for internal exposure due to non-bone -seeking radionuclides (for example, 144 Ce), predicted doses to T-lymphocytes are very close to bone marrow doses. The model allows to quantify the correction factors for FISH-based doses to obtain doses to organs and tissues., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The method of fluorescence in situ hybridization (FISH) applied to peripheral blood T lymphocytes is used for retrospective dose estimation, and the results obtained from the analysis of stable chromosomal aberrations are usually interpreted as a dose accumulated in the red bone marrow (RBM). However, after local internal exposure of the RBM, doses derived from FISH were found to be lower than those derived from direct measurements of radionuclides accumulated in the bodies of exposed persons. These results were obtained for people residing near the Techa River contaminated by 89,90 Sr (beta-emitters) in 1949-1956 (Chelyabinsk Oblast, Russia). A new analysis has been performed of the combined results of FISH studies (n = 178) undertaken during 1994-2012 for persons living on the Techa Riverside. Analysis confirms the lower slope of the translocation yield per Gy (8.0 ± 0.7 × 10 -3 ) for Techa residents in comparison with FISH data for donors with external exposures (11.6 ± 1.6 × 10 -3 , Tawn et al., Radiat Res 184(3):296-303, 2015). It was suggested that some portion of T cells remained unexposed, because they represented the descendants of T cell progenitors, which had migrated to the thymus before the start of 89,90 Sr intakes. To clarify this problem, the dynamics of T-cell Genera (TG), combining all descendants of specific T-cell progenitor reaching the thymus, was considered. Rates of TGs produced by RBM over different age periods of human life were estimated with the use of the mathematic model of T-cell homeostasis (Bains, Mathematical modeling of T-cell homeostasis. A thesis submitted for the degree of Doctor of Philosophy of the University College London. http://discovery.ucl.ac.uk/20159/1/20159.pdf , 2010). The rate of TG loss during the lifetime was assumed to be very small in comparison with production rate. The recirculation of mature T lymphocytes in contaminated RBM was taken into account. According to our model estimates, at the time of blood sampling, the fraction of exposed T lymphocytes (whose progenitors were irradiated) ranged from 20 to 80% depending on the donors' age at the start of exposure to 89,90 Sr. Dose to T lymphocytes, estimated from FISH studies, should be about 0.6-0.9 of RBM dose for residents of the upper Techa region and about 0.4-0.8 in the middle Techa region. Our results could explain the lower value of translocation yield per Gy obtained for Techa residents. The approaches for further model improvement and validation are discussed in this paper.

Release of liquid radioactive waste into the Techa River from the Mayak Production Association during 1949-1956 resulted in a significant exposure of about 30000 people who lived in downstream settlements. The residents were exposed to internal and external radiation. The article discusses the capability of two methods that were used 50 years after the termination of radioactive discharges for the dose reconstruction, namely EPR measurements of tooth enamel, and FISH measurements of stable chromosome aberrations in circulating lymphocytes. The Main issue in the application of these methods for the dose reconstruction was local irradiation from strontium radioisotopes incorporated in teeth and bones. The EPR and FISH assays were supported by measurements of the 90Sr content in the skeleton and teeth in order to estimate and subtract internal doses from incorporated 89, 90Sr. The resulting dose estimates obtained from EPR and FISH mea- surements were found to be consistent The settlement-averaged values in the upper-Techa Region varied from 550-570 mGy to 130-160 mGy and showed a reduction with the distance from the release site. The EPR- and FISH-based dose estimates were in agreement with the doses calculated with the dosimetry system TRDS that uses data on radionuclide contamination of the Techa River floodplain and individual residential histories.

Waterborne radioactive releases into the Techa River from the Mayak Production Association in Russia during 1949-1956 resulted in significant doses to about 30,000 persons who lived in downstream settlements. The residents were exposed to internal and external radiation. Two methods for reconstruction of the external dose are considered in this paper, electron paramagnetic resonance (EPR) measurements of teeth, and fluorescence in situ hybridization (FISH) measurements of chromosome translocations in circulating lymphocytes. The main issue in the application of the EPR and FISH methods for reconstruction of the external dose for the Techa Riverside residents was strontium radioisotopes incorporated in teeth and bones that act as a source of confounding local exposures. In order to estimate and subtract doses from incorporated (89,90)Sr, the EPR and FISH assays were supported by measurements of (90)Sr-body burdens and estimates of (90)Sr concentrations in dental tissues by the luminescence method. The resulting dose estimates derived from EPR to FISH measurements for residents of the upper Techa River were found to be consistent: The mean values vary from 510 to 550 mGy for the villages located close to the site of radioactive release to 130-160 mGy for the more distant villages. The upper bound of individual estimates for both methods is equal to 2.2-2.3 Gy. The EPR- and FISH-based dose estimates were compared with the doses calculated for the donors using the most recent Techa River Dosimetry System (TRDS). The TRDS external dose assessments are based on the data on contamination of the Techa River floodplain, simulation of air kerma above the contaminated soil, age-dependent lifestyles and individual residence histories. For correct comparison, TRDS-based doses were calculated from two sources: external exposure from the contaminated environment and internal exposure from (137)Cs incorporated in donors' soft tissues. It is shown here that the TRDS-based absorbed doses in tooth enamel and muscle are in agreement with EPR- and FISH-based estimates within uncertainty bounds. Basically, this agreement between the estimates has confirmed the validity of external doses calculated with the TRDS.

Fluorescent in situ hybridisation analysis of stable translocations was performed for 26 residents living along the Techa River (Russia), who were predominantly (95%) exposed to ingested strontium radioisotopes ((89)Sr and (90)Sr) resulting in exposure of their red bone marrow (RBM). Analysis was conducted at the Urals Research Center for Radiation Medicine, Public Health England and Leiden University Medical Center. Each laboratory scored 1000 cells per donor, which resulted in ∼1000 genome equivalents (GE) per donor. The age-dependent spontaneous level of translocations for each donor was evaluated on the basis of data published by Sigurdson et al. (International study of factors affecting human chromosome. Mutat. Res. 2008;652: :112-121). Reconstruction of doses was performed with the 'Techa River Dosimetry System' developed in 2009. In the studied donors, the range of individual cumulated RBM dose was from 0.3 to 3.7 Gy. Analysis of the yield of stable translocations dependent on the individual RBM dose from (89,90)Sr showed a linear dose-response relationship of 0.007 ± 0.002 translocation/GE cell/Gy (R = 0.61, p = 0.001). This set of results was in a good agreement with the previous data reported for 18 donors by Vozilova et al. (Preliminary FISH-based assessment of external dose for residents exposed on the Techa River., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This paper presents the results of a cytogenetic study conducted among residents of the Techa Riverside communities (Southern Urals, Russia) exposed in the early 1950s as a result of releases of liquid radioactive wastes from the Mayak plutonium-production facility. The study was performed 50-60 years after the beginning of the exposure for those individuals who were predominantly exposed to strontium radioisotopes ((89,90)Sr) through drinking contaminated river water and consumption of local foodstuff. Standard cytogenetic methods were used for evaluation of the frequency of unstable chromosome aberrations in exposed persons as well as in persons from the control group who were of similar age and sex, living in similar socio-economic conditions in non-contaminated territories of the Southern Urals. The exposure doses were reconstructed for the studied donors using the Techa River Dosimetry System developed in 2009. The doses of internal exposure from ingested radionuclides were evaluated using individual or family in vivo measurements of (90)Sr-body burden. Individual cumulative absorbed doses in red bone marrow (RBM) in the studied persons varied in the range of 0.01-4.4Gy. A significantly higher level of unstable chromosome aberrations (UCA) in T-cells was observed in the group of exposed individuals as compared to control group. The highest UCA level was detected in the individuals who were suspected of having chronic radiation syndrome., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This paper presents the results of a feasibility cytogenetic study using the fluorescence in situ hybridization (FISH) translocation assay for residents of villages located on the Techa River (Southern Urals, Russia) contaminated with liquid radioactive wastes from the Mayak plutonium facility in 1949-1956. The study was conducted with two groups of donors that differed in their main pathways of exposure. The first group comprised 18 residents of the middle Techa region who were exposed predominantly from ingestion of radionuclides (mostly (89,90)Sr) via the river water and local foodstuffs. The second group included 20 residents of Metlino, the closest village to the site of releases, who were exposed to external γ radiation from the contaminated river bank and exposed internally from dietary intake of radionuclides. A significant linear dependence between the radiation-induced translocation frequency and individual red bone marrow dose from incorporated (89,90)Sr, calculated with the Techa River Dosimetry System (TRDS), was found in the first group of donors. This allowed us to take the contribution of (89,90)Sr to the total radiation-induced translocation frequency into account for the second group of donors and to analyze translocations resulting from external γ-ray exposure. Individual doses from external exposure derived from the corrected translocation frequency for the second group of donors (Metlino residents), using a linear dose-response coefficient of 0.015 translocation/cell/Gy recommended by Edwards et al. in 2005, were shown to vary up to 2.1 Gy, with an average value of 0.48 Gy, which was in agreement with TRDS-based external dose estimates for Metlino residents.

The parameters characterizing the state of hemopoietic cells obtained from chronically exposed residents of the Techa riverside villages studied at late time after the exposure included: the level of somatic mutations in the TCR gene, the level of chromosome aberrations, the intensity of peripheral blood lymphocyte apoptosis. Exposed versus unexposed subjects (controls) showed an increased frequency of CD3-CD4+ T-lymphocytes, chromosome aberrations of stable type (translocations) and unstable type (dicentrics, rings), and also increased intensity of lymphocyte apoptosis. The findings of tests using a standard additional gamma-irradiation (1 Gy) accompanied by 24-hour incubation indicated that the rate of apoptosis of lymphocytes was significantly higher in exposed individuals in comparison with unexposed ones. It was suggested basing on the obtained data that at late time the chronic (for over 50 years) exposure at RBM doses from 0.01 to 3.22 Sv was a factor inducing the damage to the genetic apparatus of hemopoietic cells. Evidently, the initial chronic low-intensity irradiation in the above-indicated dose range activates adaptive processes at the cellular level in hemopoietic cells. Late time after the onset of exposure the adaptation reserves are depleted in chronically exposed persons which brings about its failure in the case of a challenge by additional external exposures.

The evaluation of remote cytogenetic consequences was studied in population, irradiated at low level during 40 years and more preferentially internally. Mean level of exposure was in 1950 year at maximum--0.2 Sv/year. In 1993 year it was equal 1.95 mSv/year. It was revealed statistically significant increasing of chromosome type of aberrations in lymphocytes of irradiated people in comparison with control ones. The incidence of chromosome type exchanges in irradiated individuals comprised 0.43 per 100 cells, and 0.17 per 100 cells in the control.

This article discusses the most important information on health effects in the Urals region (Russia) of residents exposed to radiation from activities of a weapon plutonium separation plant. The population residing on the contaminated territory was exposed to chronic combined irradiation (external gamma-irradiation and internal irradiation due to Sr-90 and Cs-137). The red bone marrow (RBM) was the critical organ affected as a result of radiation events in the Urals. In the early period, after the discharges of radioactive wastes into the river Techa (about 3 M Ci) started, cases of chronic radiation sickness (CRS; 940 cases, in total), postirradiation reactions manifested by changes in blood parameters (e.g., leukopenia, thrombocytopenia, granulocytopenia), nervous system disorders, immunity changes and ostealgic syndrome were registered in a portion of those riverside village residents who had received the highest doses. Increased leukemia and cancer mortality and morbidity rates were noted among this population in later periods. No late effects were observed in residents exposed to an explosion in a radioactive waste depot in September, 1957 when radioactive wastes with about 20 M Ci of activity were released into the environment. Similarly, the offspring of the residents exposed on the Techa also did not display any late effects. The data about the possibilities of long-term (43-45 years after the start of exposure) biological indication of chronic internal exposure are presented. The methods used in the study include in situ fluorescent hybridization, analysis of mutations in the TCR gene of peripheral blood lymphocytes and erythrocyte mutations in the glycophorine A system. No dependence of genomic translocations and mutations in glycophorine A on cumulative exposure dose to RBM was traced.