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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.