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A biologically motivated dynamical model of the lymphocytopoietic system in irradiated humans is applied here to analyze the data obtained under hematological examinations of residents of Techa riverside villages. Those people were exposed to chronic irradiation with varying dose rates, due to the radioactive contamination of the river basin by the Mayak Production Association. Modeling studies revealed the relationship between the dynamics of the lymphocytopoietic system in the examined individuals and the variation of dose rate over the considered period of time. It is found that the developed model is capable of reproducing the decreased level of blood lymphocyte concentration observed during the period of maximum radiation exposure, the recovery processes in the system observed during the period of decreasing dose rate, as well as the enhanced mitotic activity of bone marrow precursor cells in this hematopoietic lineage observed during the entire period under consideration. Mechanisms of these effects of chronic irradiation on the human lymphocytopoietic system are elucidated based on the applied model. The results obtained demonstrate the efficiency of the developed model in the analysis, investigation, and prediction of effects of chronic irradiation with varying dose rate on the human lymphocytopoietic system. In particular, the developed model can be used for predicting any radiation injury of this vital system in people exposed to chronic irradiation due to environmental radiological events, such as anthropogenic radiation accidents or radiological terroristic attacks.

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.)

Presented in the manuscript are the results of an analytic study on the chronic radiation syndrome (CRS) among 940 residents of the Techa riverside villages. The uniqueness of this pathology is associated with the fact that, so far, this clinical entity has mainly been observed among Mayak PA workers and residents of the Techa riverside villages. The analyses of CRS cases identified among a population characterised by significant heterogeneity in terms of age, baseline health status and other radiosensitivity modification factors presents a considerable scientific and practical interest. It has been shown that a long-term total exposure at doses in excess of the threshold organ dose in people causes primarily functional changes (neutropaenia, thrombocytopaenia, vegetative dysfunction and asthenia) which, if the exposure continues, are transformed into organic changes (bone marrow hypoplasia, organic damage to the nervous system). If the dose rate decreases below the threshold, a complete repair of the functional changes is observed, while organic alterations may persist for a long time.

This research has been conducted to study the activity of apoptosis of peripheral blood lymphocytes (PBLs) and the frequency of CD3-/CD4+ PBLs in people who have suffered chronic low-intensity radiation exposure. An increase in the frequency of apoptotic cells (TUNEL) is demonstrated in the group of exposed individuals relative to the control group. The frequency of mutations in the gene of the T-cell receptor in the exposed individuals is also elevated. Analyses of the mean values of apoptosis and CD3-CD4+ PBLs in different dose subgroups have found an increase in the proportion of cells with mutant T-cell receptors against the background of a decrease in the frequency of apoptotic cells in the range of low and medium radiation doses.

This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further., (Copyright © 2012. Published by Elsevier Ltd.)

The major goal of this study is to investigate and quantitatively describe the nature of the relationship between the characteristics of chronic exposure to ionizing radiation and specific patterns of hematopoiesis reduction. The study is based on about 3,200 hemograms taken for inhabitants of the Techa riverside villages over the years 1951-1956, i.e., the period characterized by a gradual decrease in dose rates. The mean cumulative red bone marrow dose was 333.6 + or - 4.6 mGy. The approach to statistical analyses involved both empirical methods and modeling (generalized linear models and logistic regressions). The results of the analyses highlighted a gradual increase in the frequency of cytopenias with dose rate. The impact of exposure on hematopoiesis reduction patterns was found to be more substantial than that of age and health status. Dose rates resulting in a two-fold increase in the frequency of cytopenias have been estimated.

A new model of the hematopoietic system for humans chronically exposed to ionizing radiation allows for quantitative description of the initial hematopoiesis inhibition and subsequent increase in the risks of late stochastic effects such as leukemia. This model describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the three blood cell types (leukocytes, erythrocytes, and platelets). The model parameters are estimated from the results of other experiments. They include the steady-state numbers of hematopoietic stem cells and peripheral blood cell lines for an unexposed organism, amplification parameters for each blood cell line, parameters describing the proliferation and apoptosis, parameters of feedback functions regulating the steady-state numbers, and characteristics of radiosensitivity in respect to cell death and non-lethal cell damages. The dynamic model of hematopoiesis is applied to the data on a subcohort of the Techa River residents with hematological measurements (e.g., blood counts) performed in 1950-1956 (which totals to about 3,500 exposed individuals). Among well-described effects observed in these data are the slope values of the dose-effect curves describing the hematopoietic inhibition and the dose rate patterns of the fractions of cytopenic states (e.g., leukopenia, thrombocytopenia). The model has been further generalized by inclusion of the component describing the risk of late stochastic effects. The risks of the development of late effects (such as leukemia) in population groups with specific patterns of early reactions in hematopoiesis (such as leukopenia induced by ionizing radiation) are investigated using simulation studies and compared to data.

The major goal of this study was to identify and quantitatively describe the association between the characteristics of chronic (low-dose rate) exposure to (low LET) ionizing radiation and cellularity of peripheral blood cell lines. About 3,200 hemograms (i.e., spectra of blood counts) obtained over the years of maximal exposure to ionizing radiation (1950-1956) for inhabitants of the Techa River were used in analyses. The mean cumulative red bone marrow dose (with standard errors), calculated using Techa River Dosimetry System-2000, was 333.6 +/- 4.6 mGy (SD = 259.9 mGy, max = 1151 mGy) to the year 1956. The statistical approach included both empirical methods for estimating frequencies of cytopenic states of the investigated blood cell lines (e.g. neutrophile, platelets, erythrocyte, etc.), and regression methods, including generalized linear models and logistic regressions which allowed taking into account confounding factors (e.g., attained age, age at maximal exposure, presence of concomitant diseases, and demographic characteristics). The results of the analyses demonstrated hematopoiesis inhibition manifested by a decrease in peripheral blood cellularity and an increase in the frequency of cytopenia in all blood cell lines (leukocytes, including lymphocytes, monocytes, neutrophiles, as well as platelets and erythrocytes). The intensity of hematopoiesis inhibition in the period of maximal exposures is determined by the combined influence of the dose rate and cumulative dose. The contribution of specific confounding factors was quantified and shown to be much less important than dose characteristics. The best predictor among dose characteristics was identified for each blood cell line. A 2-fold increase in dose rate is assumed to be a characteristic of radiosensitivity and a quantitative characteristic of the effect.

Background: This is the first analysis of solid cancer incidence in the Techa River cohort, a general population of men and women of all ages who received chronic low-dose rate exposures from environmental radiation releases associated with the Soviet nuclear weapons programme. This cohort provides one of the few opportunities to evaluate long-term human health risks from low-dose radiation exposures., Methods: Cancer incidence rates in this cohort were analysed using excess relative risk (ERR) models. The analyses make use of individualized dose estimates that take into account residence history, age and other factors. Cases are identified on the basis of continuing, active follow-up of mortality and cancer incidence., Results: Based on 1836 solid cancer cases with 446 588 person years accrued over 47 years of follow-up, solid cancer incidence rates were found to increase with dose and about 3% of the cases were attributable to radiation exposure. The ERR was 1.0/Gy (P = 0.004 95% CI (0.3; 1.9) in a linear dose-response model. There was no significant non-linearity in the dose response and no indication of effect modification by gender, ethnicity, attained age or age at first exposure., Conclusions: The Techa River cohort provides strong evidence that low-dose, low-dose rate exposures lead to significant increases in solid cancer risks that appear to be linear in dose. The results do not suggest that risks associated with low-dose rate exposures are less than those seen following acute exposures such as were received by atomic bomb survivors.