Techa Riverside Research Articles

Spectrum of TP53 Sequence Variants on Chronically Exposed Humans

It is known that ionizing radiation can damage the genetic apparatus of a cell not only through direct exposure, but also through the induction of oxidative stress. Thus, oxidation of guanine (G) nitrogenous base by oxidative stress products can result in G:CT:A and G:CC:G type transversions in the tumor growth suppressor gene TR53. Somatic and inherited variants of the TP53 gene, in its turn, are of great importance in the development of malignant neoplasms. Therefore, the aim of the study was to analyze the G:CT:A and G:CC:G transversions of the TP53 gene in peripheral blood cells of individuals affected by chronic low-dose rate exposure. The paper presents the results of the analysis of the spectrum of TP53 gene sequence variants based on G:CT:A and G:CC:G transversions in peripheral blood cells of the Techa riverside residents of the Chelyabinsk and Kurgan Oblasts, affected by chronic low-dose rate exposure in the 1950s. The range of individual values of the accumulated absorbed dose to red bone marrow due to external gamma radiation and ⁹⁰Sr ranged from 2.1 to 2742.0 mGy (mean value – 605.4 ± 191.9 mGy (M ± SE)). As a result of the study, 7 different variants of the TP53 gene based on the G:CT:A and G:CC:G transversions, which are single nucleotide replacements, were identified in the examined individuals. All detected variants were present in the IARC TP53 Database and had no clinical significance as “pathogenic” or “probably pathogenic”. Differences in the frequencies of carriers of detected TP53 gene variants between the comparison group and the main group did not reach a statistically significant level/ were not statistically significant.

Оценка влияния хронического радиационного воздействия на потерю теломерных участков хромосом в Т-лимфоцитах у женщин

Residents of the Techa Riverside villages were chronically exposed to the wide range of doses more than 60 years ago. Telomeric regions of metaphase chromosomes in the cultured peripheral blood T-lymphocytes were the subject of the research. The study aimed to assess the impact of chronic exposure on telomere loss in exposed women of the Southern Urals using a fluorescent staining method. Chromatid and chromosome telomere loss was determined in three dose subgroups: comparison group (0–0.01 Gy), group of exposed individuals with the dose of 0.2–0.9 Gy, and group of the exposed individuals with the dose of 1–4.6 Gy. In the sample of female residents of the Southern Urals chronically exposed in the range of absorbed doses to RBM of 0–4.6 Gy, it was shown that there were no differences in telomere loss between the comparison group and the group exposed to the dose exceeding 1 Gy (p > 0.33), while the group of individuals exposed to medium doses of 0.2–0.9 Gy was statistically significantly different (p < 0.05). Statistically significant differences between all groups were reported for chromosome telomere loss (p < 0.05). According to the data obtained, telomere loss was found in 99.85% of donor cells. The loss of telomere region on one of the chromatids occurred statistically significantly more often in all the groups. Thus, in the group exposed to the dose of 0.2–0.9 Gy, the average rate of chromatid telomere loss was higher, it was statistically significantly different from that of the other groups of females of the studied age.

Expression of genes SPI1 and GATA3 and Т-helpers subpopulation combination in chronically exposed people

Introduction. The influence of adverse factors including ionizing radiation leads to a violation of key transcription factors expression and the ratio of the main types of T-helper cells, which in turn initiates a wide range of immunopathological disorders.Objective. The objective of this research was to study the mRNA expression of the SPI1 and GATA3 genes, as well as the composition of T-helper type 1 and 2 subpopulations, in chronically exposed people during the period of radiation exposure late effects development.Mаterials and methods. The study was carried out on peripheral blood mononuclear cells obtained from 98 residents of the Techa riverside settlements. Two study groups were formed: the group of exposed individuals (average accumulated dose for the red bone marrow radiation was 706.8±62.7 mGy) and the comparison group (radiation dose did not exceed 70 mGy). The median age of the studied individuals at examination was 71.1 ± 0.9 years (58–87 years). The relative mRNA content of the studied genes was assessed using real-time PCR. The number of T-helpers of types 1 and 2 in the populations of T-helpers of central and effector memory was calculated using the flow cytometry method.Results. There was a decrease in the absolute and relative number of type 2 T-helpers included in the T-helpers of central memory in chronically exposed individuals. In people with accumulated doses ≥1000 mGy, an increase in the Th1/Th2 ratio of T-helpers of the central memory (p=0.01), as well as the positive correlation relationship between the relative content of type 2 T-helpers of the effector memory and the expression of the GATA3 gene were registered relative to unexposed individuals.Conclusions. The obtained results indicate that changes in the composition of T-helper cell subpopulations in chronically exposed individuals are not pronounced in the long-term period. However, these changes may directly depend on the total absorbed dose, which in turn determines the prospects for further analysis of the health status of people exposed to chronic high-dose radiation.

Conversion from the frequency of chromosome translocations in T-lymphocytes to the bone marrow dose in the long-term period after internal 89,90 Sr exposure

Cytogenetic Fluorescence In Situ Hybridization studies, that allow assessing the frequency of stable chromosome aberrations in circulating T lymphocytes, are commonly used in retrospective dosimetry in cases of uniform whole-body exposure. In the event of 89,90Sr exposure, interpretation of cytogenetic data is challenging, especially if blood sampling occurs long after the start of exposure. The weighted average dose to T-lymphocytes at the time of donor blood sampling in the long-term period after exposure to 89,90Sr does not coincide with the red bone marrow dose. Previously, we developed a model that allows us to estimate the weighted average doses to T-lymphocytes upon 89,90Sr ingress into the body of people belonging to various age groups. In this study, the modeling results were used to estimate the conversion factors from the frequency of translocations to the red bone marrow dose, which is important for assessing radiobiological effects associated with hematological diseases. The objective of our study is to estimate numerically the conversion factors (Brbm) from the dose to lymphocytes to the dose to red bone marrow for various scenarios of 89,90Sr ingestion depending on age, sex, and time after the start of exposure. The following scenarios are considered: single, uniform chronic for six months, uniform chronic for 1-5 years, non-uniform intake for 5 years (simulates the dynamics of intake in the Techa riverside settlements in 1950-1954). As a result, it has been found that the Brbm values significantly depend on the age at the time of 89,90Sr intake. The older the person is at the start of exposure, the more the cytogenetic dose differs (it is significantly lower) from the dose to the red bone marrow. We can say that the cytogenetic dose corresponds to the red bone marrow dose only in newborns and infants. This is due to the age-related dynamics of T-cell populations. Sex does not have a significant effect on Brbm. The effect of the 89,90Sr intake duration on Brbm is the most pronounced for 15-year-old adolescents. For them, the difference in Brbm values for a single and chronic 5-year ingress reaches 13%. Non-uniform intake of 90Sr over several years does not have a significant effect on Brbm and can be modelled by a uniform intake of the same duration.

ВЛИЯНИЕ ФАКТОРОВ РАДИАЦИОННОЙ И НЕРАДИАЦИОННОЙ ПРИРОДЫ НА КОНЦЕНТРАЦИЮ ТBX21 В ЛИЗАТАХ МОНОНУКЛЕАРОВ, СТИМУЛИРОВАННЫХ МИТОГЕНОМ

Purpose: To evaluate the effect of radiation and non-radiation factors on the intracellular concentration of the ТBX21 transcription factor in peripheral blood PHA-stimulated mononuclear cells of chronically exposed residents of the Techa Riverside settlements in the long-term period after the start of exposure. Material and methods: The main group consisted of 30 people aged 67–80 years with the mean dose to the red bone marrow 867±136 mGy, to thymus and peripheral lymphoid organs 125±20 mGy. The comparison group included 10 unexposed people aged 63–82 years. The main and the comparison groups had similar sex and ethnic composition. Peripheral blood mononuclear cells were PHA-stimulated for 24 hours. Cellular lysates were normalized by total protein concentration prior to being used for ELISA test. Results: After 24 hours of incubation the median and interquartile range of the intracellular TBX21 concentration in mononuclear cells was 34.2 (6.6–86.0) pg/ml after the mitogen stimulation, and 0 (0–24.9) pg/ml – without mitogen stimulation (р=0.001). In the comparison group these values made up 24.8 (0.2–47.6) and 13.0 (0–19.2) pg/ml, respectively Conclusion: The intracellular TBX21 concentration after 24-hour mitogen stimulation did not differ statistically significantly in chronically exposed and unexposed people, as well as in people from different dose groups. Statistically significant increase in TBX21 concentration in the lysates of mononuclear cells that were PHA-stimulated for 24 hours relative to non-mitogen stimulated cells was noted in chronically exposed people with medium and high doses to the red bone marrow. No correlation was revealed between the TBX21 concentration and dose characteristics, sex, and ethnicity of the studied individuals. The results are preliminary.

Влияние хронического облучения на концентрацию белка FOXP3 в лизатах митоген-стимулированных мононуклеаров крови

Disruptions of the Treg differentiation and functioning processes can play one of the crucial roles in the pathogenesis of radiation-induced malignant neoplasms in residents of the Techa riverside villages, who were chronically exposed in the low-to-medium dose range with predominant damage to the red bone marrow (RBM). This study aimed to determine the effect of radiation exposure, gender, age at the time of examination, and ethnicity on concentration of FOXP3 protein in lysates of mitogen-stimulated peripheral blood mononuclear cells in chronically exposed individuals in the period of cancer effects development. The main group consisted of 30 people aged 67–80 years, predominantly female and Turks. The comparison group included 10 unexposed individuals of similar age, gender, and ethnicity. In the main group, the mean dose to RBM was 867 mGr, to the thymus and peripheral lymphoid organs — 125 mGr. After 24-hour in vitro PHA stimulation, mononuclears were lysed, and the concentrations of the total protein and FOXP3 (using quantitative enzyme immunoassay) were measured. Among the different dose groups, there were no significant differences in FOXP3 concentration in mitogen-stimulated mononuclears (prior to the stimulation: 0 pg/ml in the comparison group and 3.50 ± 1.50 (0–27.19) pg/ml in the main group at p = 0.349; after the stimulation, respectively: 1.54 ± 1.51 (0–15.16) pg/ml and 9.71 ± 3.86 (0–77.92) pg/ml, p = 0.512). The variability of individual values is slightly higher in the main group than in the comparison group. Preliminary results allow concluding that the dose to RBM, thymus and peripheral lymphoid organs, age at the time of examination, gender, and ethnicity have no statistically significant effect on the concentration of FOXP3 protein in the lysates of the mitogen-stimulated peripheral blood mononuclear cells of chronically exposed people.

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

Evaluation of age effect on the frequency of radiation-induced translocations, registered using FISH in circulating T-lymphocytes in the long-term period after exposure, is both of theoretical and practical interest for the purposes of biodosimetry. The objective of our study was to analyze the dose dependence of the translocation frequency in the peripheral blood T-lymphocytes in donors of different age who were exposed in the Techa Riverside settlements (n = 197). In cytogenetic studies, whole chromosome painting probes were used to stain three pairs of chromosomes. A total of 104,721 genome equivalents (GE) were calculated and 2,540 translocations were found. For each donor, the individual absorbed doses in organs and tissues at the time of blood sampling were calculated using the Techa River Dosimetry System. In addition, doses to T-lymphocytes and their progenitors were calculated using the innovative modelling approach with due account of age related-dynamics of T-lymphocytes. The age dependence of the translocation frequency was associated particularly with these doses. The main sources of donor exposure were 89,90Sr, accumulating in bones and irradiating the bone marrow almost locally. To assess the parameters of the dose-effect relationship, linear regression model was used. After taking into account background values, the lowest frequency of translocations per 1000 GE per Gy was found in donors aged 0–5 years at the time of exposure (9.3 ± 1.3), which is statistically significantly lower than in children aged 6–18 years (15.3 ± 1.5), but not in adults (11.9 ± 2.9). The value for adults (18 years) was characterized by the maximum scatter, but was close to the values obtained in an international study of nuclear enterprise personnel after external exposure (11.6 ± 1.6). The values of the background translocation frequencies registered in various age groups correspond to the published data obtained in a joint international study on unexposed donors. We have also confirmed the absence of sex-effect on the frequency of translocations.

Анализ связи полиморфного локуса rs1052133 гена OGG1 с риском развития злокачественных новообразований у людей, подвергшихся радиационному воздействию

Genetic predisposition without doubt is one of the risk factors of cancer initiation. It is known that single nucleotide polymorphisms (SNP) of genes that maintain the genome stability, including SNP of DNA repair, may contribute to the initiation of carcinogenesis. Single-nucleotide polymorphisms of genes that support genome stability, including SNP of DNA repair genes, can contribute to cancer initiation. Polymorphism of the excision repair gene OGG1 causes interest of leading scientific groups from various countries. It is assumed that there is relationship between the rs1052133 polymorphism in the gene and predisposition to cancer initiation. The objective of this study was to establish association between rs1052133 polymorphism of base excision repair gene OGG1 and the risk of cancer initiation in people chronically exposed to ionizing radiation. Residents (888 people) of the Techa riverside settlements, chronically exposed to low or medium radiation from the Techa River and the East-Urals Radioactive Trace were included in the study. The study allowed researchers to establish that exposed to chronic radiation people, carriers of the rs1052133*G allele have increased risk of malignant neoplasms initiation: OR=1.38; 95% CI [1.05-1.83], p=0.023. The multifactorial synergistic interactions between the dose to the red bone marrow and the rs1052133 polymorphism of the OGG1 gene was found: Testing Balanced Accuracy (TBA)=0.56; Cross Validation Consistency (CVC)=10/10; p=0.01). The study found that the rs1052133 polymorphism may be considered as genetical marker of risk of cancer initiation in people, chronically exposed to radiation with doses ranged from 0.74 to 3507.07 mGy (average 523.10+/-33.89 mGy). It was found that the presence of the rs1052133*G in combination with radiation exposure can modify the risk of solid cancers initiation, as it is indicated by the synergistic relationship between the SNP and the radiation dose.

Association Between Single Nucleotide Polymorphisms of Apoptosis and Cell Cycle Control Genes and the Risk of Cancer Development in Chronically Exposed Persons

The objective of the paper was to study the association between single nucleotide polymorphisms of genes involved in the cell cycle control (ATM rs664677, MDM2 rs2279744, CDKN1A rs1801270) and apoptosis (BCL-2 rs2279115, BAX rs4645878, TNFα rs361525) and the risk of solid cancer development in persons of different ethnicity exposed to chronic radiation. The study included 915 residents of the Techa riverside settlements belonging to two ethnic groups (Slavs and Turks) who were affected by chronic low dose rate exposure in the low to and medium dose range. 310 persons out of them had solid cancers. Genotyping of polymorphic regions of genes regulating cell cycle and apoptosis was performed by real-time PCR method. The study showed that the rs2279744*C allele of the MDM2 gene was associated with an increased risk of cancer development (OR = 2.29; 95% CI 1.23–4.28; p = 0.007), while the rs1801270*A allele of the CDKN1A gene showed a protective effect against cancer development (OR = 0.55; 95% CI 0.35–0.85; p = 0.01) in exposed individuals of the Turkic ethnic group. The combined effect of the identified polymorphisms and soft tissue exposure dose statistically significantly modifies the risk of cancer development in chronically exposed persons of the Turkic ethnic group, with the greatest contribution being made by the carriage of the rs2279744*C allele of the MDM2 gene.

MRNA Expression of GATA3, FOXP3, TBX21, STAT3, NFKB1, and MAPK8 Transcription Factors in Humans and Their Cooperative Interactions Long-Term after Exposure to Chronic Radiation

The results of mRNA expression of the GATA3, FOXP3, TBX21, STAT3, NFKB1, and MAPK8 transcription factors in peripheral blood cells of 264 residents of the Techa riverside villages of the Chelyabinsk and Kurgan regions, who were affected by chronic low dose-rate exposure in the 1950s, are shown. The range of individual doses to the red bone marrow due to external gamma exposure and 90Sr was 77.8–3507.1 mGy, and the mean dose was 706.3±46.3 mGy. It has been found that changes in the transcriptional response of the cell occur at the molecular level in the long term after chronic exposure. A modified expression of the immunoregulatory genes NFKB1 and MAPK8 in the peripheral blood cells of exposed people was found. A comparative analysis of the interaction of the studied mRNAs demonstrated the presence of a link between the MAPK8 and NFKB1 genes in the group of chronically exposed individuals. The results obtained may indicate the involvement of these transcription factors in the impairment of the immune response in the exposed population.

Medical consequences of the Urals radiation accidents: Comparative analysis

• In 1957, liquid radioactive waste (LRW) was released into the Techa River and the explosion of the storage tank for LRW at the Mayak Production Association (Mayak PA) led to radioactive contamination and long-term public exposure of a part of the Urals region, Russia. • The countermeasures on the Techa River were insufficient and implemented with delay whereas those after the 1957 accident were immediate and more extensive. • 90 Sr-body burdens and exposure doses to red bone marrow in the residents of the Techa riverside settlements were significantly higher than those in the residents of the East Urals Radioactive Trace (EURT), and medical consequences were more severe despite the comparability of radioactivity emitted into environment. • Health damage of the Techa residents assessed by the criterion of collective effective dose was significantly higher than that of the EURT population, and it correlated with the registered early and late health effects. The paper provides comparative analysis of health effects after radioactive contamination of the Techa River and the 1957 radiation accident at the Mayak Production Association (Mayak PA) in terms of efficiency of performed protective measures. Both radiation accidents took place in the Urals Region, Russia, within a short period of time due to poor-quality of storage technology of liquid radioactive waste. Despite different pathways of radioactive contamination of the environment (air or water), similar long-term combined (external γ- and internal) exposure of the population took place. Countermeasures after the 1957 radiation accident included not only scheduled but also emergency evacuation of people. Scheduled activities on the Techa River were delayed and insufficient and resulted in exposure of local residents at doses greatly exceeding permissible levels. It also led to development of both early deterministic effects and increase in leukemia and solid cancer incidence, and mortality in the long-term period.

Undifferentiated oligophrenia in the offspring of the in-utero exposed Techa riverside residents

The objective of the work was to study the prevalence of undifferentiated oligophrenia in the offspring of antenatally exposed parents. The analysis included 2,908 offspring of the Techa River antenatally exposed residents within Chelyabinsk Oblast born in the period 1974-1992. 1,705 of them were born to an antenatally exposed mother, 1,668 – to an antenatally exposed father, and 368 – to both antenatally exposed parents. Mean in-utero dose for the cohort of in-utero exposed population was 5.8 mGy, while the mean dose of mothers of oligophrenic persons was 12.6 mGy, and that of antenatally exposed fathers – 5.3 mGy. It was found that the prevalence of oligophrenia of different degrees of severity compared to the control group, which included the offspring of unexposed persons of the same age, ethnicity and living in adjacent territories, tends to increase More than 20% of cases of moderate oligophrenia in both main and control groups were of familial nature. All cases of severe oligophrenia in the compared groups were sporadic. There was an increase (p<0.05) in the prevalence of severe oligophrenia when compared to the control group in the offspring cohort of antenatally exposed individuals, 0.45% and 0.24%, respectively, which was 0.59%, p<0.01, in the offspring of exposed mothers. The corresponding rates for the offspring of antenatally exposed fathers were 0.42% and 0.24% in the main and control groups, respectively, p>0.05. No dependence of the prevalence of oligophrenia on the maternal and paternal in-utero dose has been detected.

Субпопуляционный состав Т-хелперов в периферической крови хронически облученных лиц в отдаленном периоде

Earlier, it has been convincingly established that exposure to ionizing radiation (IR) alters the T cell-mediated immunity in the long term. However, a search for papers describing the effect chronic exposure to radiation has on various subpopulations of T-helpers yielded no results. Therefore, we designed this study seeking to investigate the quantitative characteristics of various subpopulations of T-helpers in the peripheral blood of individuals chronically exposed to low-level radiation for a long period of time. The study involved 102 chronically exposed Techa Riverside residents (Russia) aged 60–87 years. The participants were divided into two groups, one comprised of exposed individuals with the average red bone marrow (RBM) irradiation dose of 567 ± 73 mGy, another, the control group, comprised of people with the irradiation dose below 70 mGy. With the help of flow cytometry, we identified the quantitative characteristics of T-helper subpopulations in the peripheral blood at various stages of their differentiation, as well as various T-helper subpopulations of central and effector memory. The study revealed no significant differences in the composition of T-helper subpopulations in the compared groups. We discovered a significant growth of the double positive follicular T-helper 17 subpopulation in the population of central memory T-helpers, which is associated with the increase of RBM (p = 0.04; S = 0.19), thymus and peripheral lymphoid organs (p = 0.03; S = 0.22) irradiation dose. In the group of exposed individuals, the number of naive T-helpers (p = 0.009) and double positive follicular T-helpers 17 in the TEM subpopulation (p = 0.04) was decreasing as the age of participants increased, and the number of effector memory T-helpers, on the contrary, increased with age (p = 0.04). We have not registered similar phenomena in the comparison group.

East Ural Radioactive Trace: cancer mortality over a 57-year period (1957-2014)

The objective of the current study was to assess the cancer mortality risk in the cohort of the exposed population on the territory of the East Urals Radioactive Trace over a 57-year follow-up period from 1957 to 2014 using individual doses. Materials and methods: At the end of September 1957 as a result of an accident in the cooling system of storage tanks with liquid radioactive waste, an explosion occurred on the territory of the Mayak PA which led to the formation of the East Urals Radioactive Trace. The population living in the contaminated settlements of the Chelyabinsk and Sverdlovsk regions has been affected by prolonged external and internal exposure. The cohort of individuals exposed in the territory of the East Urals Radioactive Trace numbers 21,384 people, of whom 2,055 persons had lived in Techa riverside settlements before the 1957 accident and received additional radiation exposure. The mean stomach dose for members of the East Urals Radioactive Trace cohort was 36 mGy, the maximum dose was 1130 mGy. The updated TRDS-2016 dosimetry system was used to assess individualized doses. Over the 57-year follow-up period of the cohort (1957-2014), 1294 deaths from cancer were registered in the catchment area. The number of person-years at risk was 511278. The analysis of the cancer mortality risk was carried out with the EPICURE statistical package using the Poisson regression method. Confidence intervals were calculated using the maximum likelihood method. Results: In the course of the cancer mortality analysis in the East Urals Radioactive Trace cohort over a 57-year period, a statistically significant excess relative risk of mortality per 100 mGy equal to 0.05 (95% CI: 0.002; 0.11, p = 0.04) was obtained in the entire East Urals Radioactive Trace cohort. If individuals who received additional exposure on the Techa River were excluded from the analysis, the value of the risk loses its statistical significance.

Transcriptional activity of repair, apoptosis and cell cycle genes (TP53, MDM2, ATM, BAX, BCL-2, CDKN1A, OGG1, XPC, PADI4, MAPK8, NF-KB1, STAT3, GATA3) in chronically exposed persons with different intensity of apoptosis of peripheral blood lymphocytes.

Transcriptional activity of genes involved in maintaining genetic homeostasis (genes for repair, cell cycle and apoptosis: TP53, MDM2, ATM, BAX, BCL-2, CDKN1A, OGG1, XPC, PADI4, MAPK8, NF-KB1, STAT3, GATA3) was studied in chronically exposed persons with an increased intensity of early and late stages of apoptosis and necrosis of peripheral blood lymphocytes. The object of this study was peripheral blood mononuclear cells obtained from 132 chronically exposed residents of the Techa riverside villages. The mean accumulated dose to red bone marrow was 426.4 ± 48.2 mGy (1.3–2930.0 mGy), to thymus and peripheral immune organs, 58.9 ± 7.9 mGy (0.1–489.0 mGy). The study was performed more than 60 years after the onset of exposure, the average age of exposed persons was 68 ± 0.6 years (55–86 years). The study of apoptotic and necrotic death of peripheral blood lymphocytes was based on the presence of phosphatidylserine on the cell membrane surface, as well as on its permeability for DNA-intercalating dye. Evaluation of the relative content of mRNA genes for repair, cell cycle, and apoptosis was carried out using real-time PCR. An increased relative content of PADI4 gene mRNA was registered in the group of chronically exposed persons with the increased intensity of early apoptosis (p = 0.006). Modulation of the relative content of mRNA of the TP53 (p = 0.013) and BCL-2 (p = 0.021) genes was detected in the group of chronically exposed individuals with the increased intensity of the late stage of apoptosis. A statistically signif icant increase in the transcriptional activity of the TP53 gene was observed in the group of chronically exposed persons with the increased intensity of peripheral blood lymphocyte necrosis in the long-term period (p = 0.015). In the course of the study it was noted that exposed people with increased intensity of apoptosis, f irst of all, demonstrate changes in the transcriptional activity of apoptotic genes. These data are consistent with current views on the activation of programmed cell death.

Specific features of medical care provision to the population of the Techa riverside settlements

This paper is devoted to the issue of medical care provision to the residents of the Techa riverside settlements affected by long-term radiation exposure. The river was contaminated due to operational and accidental releases of liquid radioactive waste (LRW) by the ‘Mayak’ Production Association from 1949 to 1956. Contamination of the river and its floodplain with radionuclides, including long-lived 90Sr and 137Cs, caused long-term external and internal exposure of the population, predominantly of the bone marrow. Protective countermeasures (resettlement of residents, introduction of restrictions on the use of the river and floodplain, construction of wells, etc) did not manage to prevent relatively high exposure doses to the population. The mean dose value of bone marrow exposure in residents of the riverside settlements was 0.35 Gy, whereas the maximum values were up to 7.92 Gy. The first medical examinations by mobile teams of the Moscow Institute of Biophysics were started approximately two years after the onset of LRW releases. Since 1955, exposed residents have been followed up and are undergoing medical treatment at the Clinic of the Urals Research Center for Radiation Medicine of the Federal Medical and Biological Agency (URCRM). This center was established in response to the necessity to study the biological effects of the combined external γ-exposure and exposure due to 90Sr in order to arrange medical care for the exposed population. The URCRM Clinic focuses on the provision of hematological care since cases of chronic radiation syndrome were registered among the exposed population in the early period, and increased leukemia incidence has been observed in the long-term period.

Пул гемопоэтических стволовых клеток в периферической крови хронически облученных лиц в отдаленном периоде

Changes in the peripheral blood cellular composition were observed in the long term period in the residents of the Techa riverside villages chronically exposed to radiation, which may be the consequence of structural and functional disorders in the pool of hematopoietic stem cells (HSC) and progenitor cells. Therefore, the study was aimed to quantify peripheral blood CD34+ cell pool in individuals chronically exposed to radiation over a long-term period. Sixty years after the onset of exposure, a total of 153 individuals were examined, who were divided into four groups: individuals exposed in utero and postnatally (the average postnatal absorbed dose was 570 mGy); individuals exposed only postnatally (the average postnatal absorbed dose was 790 mGy), and two comparison groups, in which the average postnatal absorbed dose to red bone marrow did not exceed 70 mGy. Absolute and relative peripheral blood CD34+ cell counts in chronically exposed individuals were assessed by flow cytometry. No changes in CD34+ cell counts compared to comparison group were revealed in the group of individuals exposed in utero and postnatally; no age-related changes were registered as well. However, a significant decline in absolute HSC and progenitor cell counts with increased absorbed dose to red bone marrow was observed. In the group of individuals exposed only postnatally, there was a significant increase in peripheral blood CD34+ cell counts compared to comparison group (p = 0.004 for absolute cell count; p = 0.009 for relative cell count), dose-dependent increase in peripheral blood HSC and precursor cell counts (p = 0.02 for absolute cell count; p = 0.03 for relative cell count), along with age-related decline in these cells’ counts (р = 0.02 for absolute cell count; p = 0.04 for relative cell count).

ДИАГНОСТИКА ХРОНИЧЕСКОГО ЛУЧЕВОГО СИНДРОМА НА РАННЕЙ СТАДИИ

Purpose: To describe early symptoms of chronic radiation syndrome (CRS) which is of utmost importance for diagnosing this rare radiation pathology in man. 
 Material and methods: The paper presents the findings of retrospective analysis of early clinical manifestations of chronic radiation syndrome (CRS) based on the data of a long-term medical follow up of the residents of the Techa riverside communities. Mean doses of postnatal exposure to red bone marrow in patients with CRS calculated with TRDS-2016D were 698.8±18.2 mGy, maximum doses were 3 603.9 mGy.
 Results: Clinical picture of the CRS at the early stage was characterized by a set of non-specific changes including hematological, immune, neurological, and endocrine ones, as well as impairment of functions of a number of internal organs. The above-mentioned CRS symptoms developed in a certain sequence and depended on dose rate and absorbed dose to the organs. Prior to the development of a full-scale CRS clinical picture patients had a decrease in olfactory and taste thresholds, in vibration sensitivity, and changes in systemic immunity. Impairment of hematopoiesis, nervous and endocrine systems were also noted even at the early stage of CRS. Initial CRS changes were moderate and transient. The analysis of early CRS symptoms allows assuming that early CRS stage is a dysregulation pathology that is caused initially by radiation-induced disorders of immunohematopoiesis, nervous and endocrine systems. Visceral changes at the early CRS stage are secondary and functional. If exposure is terminated, they are reversible. However, if exposure continues at doses high enough to cause morphological changes in organs and tissues (dystrophy, fibrosis, hypoplasia, etc.), CRS course worsens and becomes irreversible.
 Conclusion: It was demonstrated that CRS diagnosis at the early stage is very complicated. The key issue is to analyze the relationship of specific CRS symptoms development and dose rate and absorbed organ doses.

Early signs of chronic radiation syndrome in residents of the Techa riverside settlements.

The review presents the results of a retrospective analysis of early markers of chronic radiation syndrome (CRS) in residents of the Techa riverside settlements. Mean values of postnatal red bone marrow doses calculated with the Techa River Dosimetry System-2016D were 698.8 ± 18.2mGy, and maximum values reached 3 603.9mGy. The clinical picture of the initial CRS stage was characterized by a set of non-specific functional changes that included not only hematopoietic but also immune, neurological, endocrine, and visceral disorders. CRS signs developed in a certain sequence. The earliest CRS signs were: increase of olfactory and taste thresholds, decrease of sensitivity to vibration and changes of systemic immunity. These were registered prior to hematopoietic changes typical of CRS. All initial organ changes related to CRS were functional in nature, mild or moderate, and transient. Early changes induced by chronic exposure in nervous, immune, and endocrine systems permit to consider CRS at early stages as a stereotype dysregulation pathology primarily based on radiation-induced disorders in regulatory systems. Disorders of circulatory, digestive, and other organs at early stages of CRS are secondary and their function restores spontaneously when the exposure stops. If exposure is continuous at doses sufficient for development of morphological tissue changes (dystrophy, fibrosis, hypoplasia and others), the CRS course becomes progressive and irreversible. The paper also describes the specific clinical manifestations of early stage of CRS in children.

Study of the DNA Damage in Peripheral Blood Lymphocytes Using Micronucleus Test in Residents of the Techa Riverside Villages Who Were Chronically Exposed in Utero and Postnatally

The paper presents the results of the assessment of the frequency of the peripheral blood Т lymphocytes with micronuclei in Techa riverside residents who were chronically exposed in the 1950s. The study was performed 40–60 years after the onset of exposure. The exposed persons consisted of two groups: individuals who were first exposed in utero and then postnatally, and individuals who had only postnatal exposure. Cumulative dose to RBM in exposed persons varied within the range 0.001–4 Gy. A comparison group was also formed. It included individuals comparable in age, sex, and living conditions, but these people were not affected by accidental exposure. Findings of the study demonstrated that the frequency of lymphocytes with micronuclei was significantly higher in exposed women as compared to exposed men. The frequency of lymphocytes with micronuclei was significantly lower in those exposed in utero relative to the postnatally exposed persons and members of the comparison group. This decrease was observed both in women and in men. The study of the contribution of the cumulative dose to RBM revealed an increase in frequency of the lymphocytes with micronuclei in women exposed at doses of 0.1–0.49 Gy.