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A new model of the hematopoietic system response in humans chronically exposed to ionizing radiation describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the four blood cell types (lymphocytes, neutrophiles, erythrocytes, and platelets). The required model parameters were estimated based on available results of human and experimental animal studies. They include the steady-state number of hematopoietic stem cells and peripheral blood cell lines in an unexposed organism, amplification parameters for each blood line, parameters describing proliferation and apoptosis, parameters of feedback functions regulating the steady-state numbers, and characteristics of radiosensitivity related to cell death and non-lethal cell damage. The model predictions were tested using data on hematological measurements (e.g., blood counts) performed in 1950-1956 in the Techa River residents chronically exposed to ionizing radiation since 1949. The suggested model of hematopoiesis is capable of describing experimental findings in the Techa River Cohort, including: (1) slopes of the dose-effect curves reflecting the inhibition of hematopoiesis due to chronic ionizing radiation, (2) delay in effect of chronic exposure and accumulated character of the effect, and (3) dose-rate patterns for different cytopenic states (e.g., leukopenia, thrombocytopenia).

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.

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.

Internal contamination by radionuclides may constitute a major source of exposure and biological damage after radiation accidents and potentially in a dirty bomb or improvised nuclear device scenario. We injected male C57BL/6 mice with radiolabeled cesium chloride solution (137CsCl) to evaluate the biological effects of varying cumulative doses and dose rates in a two-week study. Injection activities of 137CsCl were 5.71, 6.78, 7.67 and 9.29 MBq, calculated to achieve a target dose of 4 Gy at days 14, 7, 5 and 3, respectively. We collected whole blood samples at days 2, 3, 5, 7 and 14 so that we can publish the issue in Decemberfrom all injection groups and measured gene expression using Agilent Mouse Whole Genome microarrays. We identified both dose-rate-independent and dose-rate-dependent gene expression responses in the time series. Gene Ontology analysis indicated a rapid and persistent immune response to the chronic low-dose-rate irradiation, consistent with depletion of radiosensitive B cells. Pathways impacting platelet aggregation and TP53 signaling appeared activated, but not consistently at all times in the study. Clustering of genes by pattern and identification of dose-rate-independent and -dependent genes provided insight into possible drivers of the dynamic transcriptome response in vivo, and also indicated that TP53 signaling may be upstream of very different transcript response patterns. This characterization of the biological response of blood cells to internal radiation at varying doses and dose rates is an important step in understanding the effects of internal contamination after a nuclear event. [ABSTRACT FROM AUTHOR]