Cell Composition of Peripheral Blood in Residents of the Techa River Region Exposed to Radiation in Utero

Biology Bulletin - The results of a study on the composition of peripheral blood cells in residents of the Techa River region (Chelyabinsk oblast) who were exposed to radiation both in utero and...     

Interpretation of FISH Results in the Case of Nonuniform Internal Radiation Exposure of Human Body with the Use of Model Approach

Russian Journal of Genetics - The fluorescence in situ hybridization (FISH) technique allows for the estimation of the number of stable chromosomal aberrations (translocations) in human blood...     

New stochastic carcinogenesis model with covariates: an approach involving intracellular barrier mechanisms

In this paper we present a new multiple-pathway stochastic model of carcinogenesis with potential of predicting individual incidence risks on the basis of biomedical measurements. The model incorporates the concept of intracellular barrier mechanisms in which cell malignization occurs due to an inefficient operation of barrier cell mechanisms, such as antioxidant defense, repair systems, and apoptosis. Mathematical formalism combines methodological innovations of mechanistic carcinogenesis models and stochastic process models widely used in studying biodemography of aging and longevity. An advantage of the modeling approach is in the natural combining of two types of measures expressed in terms of model parameters: age-specific hazard rate and means of barrier states. Results of simulation studies allow us to conclude that the model parameters can be estimated in joint analyses of epidemiological data and newly collected data on individual biomolecular measurements of barrier states. Respective experimental designs for such measurements are suggested and discussed. An analytical solution is obtained for the simplest design when only age-specific incidence rates are observed. Detailed comparison with TSCE model reveals advantages of the approach such as the possibility to describe decline in risk at advanced ages, possibilities to describe heterogeneous system of intermediate cells, and perspectives for individual prognoses of cancer risks. Application of the results to fit the SEER data on cancer risks demonstrates a strong predictive power of the model. Further generalizations of the model, opportunities to measure barrier systems, biomedical and mathematical aspects of the new model are discussed.     

Cataract in the chronically exposed residents of the Techa riverside villages

The present study is based on a retrospective analysis of archive data of the Clinical Department of the Urals Research Center for Radiation Medicine that has been established to examine and treat accidentally exposed residents of the Urals Region. All individuals included in this study were examined by an ophthalmologist. The study of cataract incidence has been conducted retrospectively for the period from 1951 till 2000 among chronically exposed residents of the Techa riverside villages (6343 persons). Individual accumulated absorbed doses to soft tissues (analogue of eye dose) reached 1.18 Gy (mean 0.12 Gy) while for 88.9% of the study group the dose did not exceed 0.1 Gy. There was no evidence of the influence of low-dose and low-dose rate on cataract incidence. Excess relative risk of cataract formation per 1 Gy was 0.40 (95% CI ?0.43; 1.47). It is noted that 15% of all excess cases were registered in persons with soft tissue dose above 0.3 Gy, though their fraction among all examined persons was only 4.1%. Risk of cataract development significantly increased in exposed individuals with retinal angiosclerosis, diabetes and arterial hypertension.     

Modeling hematopoietic system response caused by chronic exposure to ionizing radiation

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).     

Mortality in the offspring of individuals living along the radioactively contaminated Techa River: a descriptive analysis

From 1949 onwards, radioactive waste was released into the Techa River in the southern Urals and the population living along the river was exposed to ionising radiation. Relocation of these people did not start until several years later, causing many individuals to be exposed to substantial doses from internal and external radiation. The identification and follow-up of the exposed individuals started more than 40 years ago and is still continuing. The Techa River offspring cohort (TROC) that has recently been established, comprises 10,459 children born to at least one parent living along the Techa River during the period 1950-1992. Of these children, 3,897 were born during the period of highest release, i.e. between 1950 and 1956 and might thus have been exposed in utero. A total of 1,103 individuals have since died mainly due to infectious and respiratory diseases, injury and poisoning. Only 25 cases were identified as having died of a malignant condition. The radioactive contamination of the Techa River in the southern Urals gives a unique possibility to study the adverse effects of protracted exposure to ionising radiation in a large well-described cohort. The Techa River offspring cohort will make it possible to study the effects on those exposed in utero or early in life and the follow-up of the cohort in the future is, therefore, of great importance. Comparisons with other cohorts of humans exposed early in life, will increase our knowledge in this field of research.     

Chronic low-dose exposure in the Techa River Cohort: risk of mortality from circulatory diseases

The aim of the present study was to analyze the mortality from circulatory diseases for about 30,000 members of the Techa River cohort over the period 1950–2003, and to investigate how these rates depend on radiation doses. This population received both external and internal exposures from ⁹⁰Sr, ⁸⁹Sr, ¹³⁷Cs, and other uranium fission products as a result of waterborne releases from the Mayak nuclear facility in the Southern Urals region of the Russian Federation. The analysis included individualized estimates of the total (external plus internal) absorbed dose in muscle calculated based on the Techa River Dosimetry System 2009. The cohort-average dose to muscle tissue was 35 mGy, and the maximum dose was 510 mGy. Between 1950 and 2003, 7,595 deaths from circulatory diseases were registered among cohort members with 901,563 person years at risk. Mortality rates in the cohort were analyzed using a simple parametric excess relative risk (ERR) model. For all circulatory diseases, the estimated excess relative risk per 100 mGy with a 15-year lag period was 3.6 % with a 95 % confidence interval of 0.2–7.5 %, and for ischemic heart disease it was 5.6 % with a 95 % confidence interval of 0.1–11.9 %. A linear ERR model provided the best fit. Analyses with a lag period shorter than 15 years from the beginning of exposure did not reveal any significant risk of mortality from either all circulatory diseases or ischemic heart disease. There was no evidence of an increased mortality risk from cerebrovascular disease (p > 0.5). These results should be regarded as preliminary, since they will be updated after adjustment for smoking and alcohol consumption.     

Tissue reactions under chronic exposure to ionizing radiation

Reviewed are radiobiological data on the emergence of tissue reactions that may determine the course and outcome of human chronic irradiation. The main mechanisms of the reaction of hemopoietic, immune, reproductive, endocrine, respiratory systems and skin to long-term and fractionated exposure to ionizing radiation are considered. The problem of developing a new approach to threshold dose estimation for chronic exposure effects is discussed.