[Methylation Status of Apoptosis Genes and Intensity of Apoptotic Death of Peripheral Blood Lymphocytes in Persons Chronically Exposed to Radiation].

Methylation of the CpG islands of gene promoter regions is the most common epigenetic modification involved in the regulation of gene expression. A number of studies have shown that ionizing radiation can cause both hyper- and hypomethylation of DNA. Aberrant methylation affects cellular processes and can lead to the development of various pathological states. In the literature, there are few studies on the methylation status of human DNA a long time after radiation exposure. Here, the methylation level of CpG islands of the promoter regions of apoptosis genes (BCL2, ATM, MDM2, CDKN1A, STAT3, and NFKB1), and also its influence on apoptosis of peripheral blood lymphocytes in chronically exposed persons were studied. Residents of the South Ural region who were chronically exposed to radiation (after discharges of radioactive wastes into the Techa river by the "Mayak Production Association" in 1949-1956) were included in the study. It was established that the proportion of individuals with hypermethylated BCL2 gene promoter among the exposed people was statistically significantly higher than in the control group. The percentage of methylation of the ATM gene promoter weakly positively correlated with dose and age characteristics. Differences in the frequency of lymphocyte apoptosis in exposed individuals with a hypo- or hypermethylated ATM gene promoter were also established. The data indicate that, in the long-term, after chronic low intensity radiation exposure at low and medium doses, epigenetic modifications of the genome occur, which are manifested as changes in methylation of promoter regions of BCL2 and ATM genes.

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-lived90Sr and137Cs, 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 to90Sr 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.

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 ± 18.2 mGy, and maximum values reached 3 603.9 mGy. 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.

Radioecological consequences of radioactive releases due to weapons-grade plutonium production at the 'Mayak' facility in the Russian Federation.

The process of nuclear weapons production from 1949 to 1987 was accompanied by the generation of a great amount of radioactive waste. Waste processing operations and controls on discharges at this time were not to the same standard as today. Because of this, vast areas of the Urals region of Russia surrounding the Mayak Production Association (MPA) were exposed to routine and accidental radioactive contamination. The greatest contribution to the contamination was gas aerosol emissions from the MPA in the 1950s (total activity 38 PBq, mainly131I), releases of liquid radioactive waste into the Techa River from 1949 to 1956 (total activity 115 PBq, including long-lived90Sr and137Cs) and accidental atmospheric releases as a result of the thermochemical explosion of the storage tank for liquid radioactive waste in 1957 (74 PBq, relatively short-lived radionuclides being the main contributors). Protective measures helped to relieve the pressing problem of population safety in the 1950s and 1960s, but they led to the appearance of new sources of contamination in the territory surrounding the MPA-Lake Karachay (total activity of beta-emitters 4400 PBq) and the Techa Cascade of Reservoirs (TCR; total activity 8 PBq). Owing to natural radioactive decay and rehabilitation measures, the radiation situation in the East Urals Radioactive Trace (EURT) has improved considerably over the years. Economic activity has been partially restored in these territories. Only the most contaminated territory of the East Urals Radioactive Reserve cannot be used for any economic activities up to the present day. Marked non-uniformity of radioactive contamination of the EURT and the Techa River floodplain, as well as radionuclide washout from Lake Karachay and the TCR into the underground waters and the Techa River require on-going radioecological monitoring, management and regulatory supervision.

Single nucleotide polymorphism and expression of genes for immune competent cell proliferation and differentiation in radiation-exposed individuals.

It is known that ionizing radiation influences the expression of the genes that play a key role in the mechanisms of maintaining the stability of cellular homeostasis. As a rule, changes in the transcriptome of an exposed cell occur within the first 24 hours following radiation exposure. And it predetermines early response in the case of genome damage. Later on modulations in gene transcription activity are also possible and could result in a carcinogenic effect. However, in order to find the role of exogenous factors (ionizing radiation), it is also necessary to take into account the contribution of endogenous factors that are able to modify gene transcription activity. This is especially important for long after the onset of radiation exposure. Single nucleotide polymorphisms located in regulatory regions of the genes may belong to this group of factors. The objective of the current study was to analyze the influence of ionizing radiation on the transcription activity of the STAT3, GATA3, NFkB1, PADI4 genes, which regulate proliferation and differentiation of immune competent human cells; and to assess the potential influence of single nucleotide polymorphisms located in regulatory regions of the genes on the amount of mRNA. The study involved people who had been chronically exposed due to releases of radioactive waste into the Techa River. It was observed that 60 years after the onset of radiation exposure changes in the transcription activity of the NFkB1 and PADI4 genes were registered in people with cumulative doses to RBM within the range 78-3510 mGy. In people who had been chronically exposed, the effect of allelic variations in rs1053023, rs4143094, rs28362491, rs874881 on the level of mRNAs of the STAT3, GATA3, PADI4, NFkB1 genes has not been established.

Immunological status of chronically exposed persons with increased level of TCR mutations.

Dose- and dose rate-dependent increase in the number of СD3+СD16+CD56+-lymphocytes and lysosomal activity of neutrophils was noted in peripheral blood of the Techa riverside residents with increased level of TCR gene-mutated T lymphocytes long after chronic exposure of predominantly red bone marrow (mean exposure dose was 0.89 ± 0.09 Gy, individual dose range was 0.09-1.96 Gy). The performed analysis showed that the above-mentioned immunological changes could be a response to an increase in the frequency of mutations (TCR mutations in particular) in the cells of exposed individuals.

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.

Consequences of the radiation accident at the Mayak production association in 1957 (the 'Kyshtym Accident').

This paper presents an overview of the nuclear accident that occurred at the Mayak Production Association (PA) in the Russian Federation on 29 September 1957, often referred to as 'Kyshtym Accident', when 20 MCi (740 PBq) of radionuclides were released by a chemical explosion in a radioactive waste storage tank. 2 MCi (74 PBq) spread beyond the Mayak PA site to form the East Urals Radioactive Trace (EURT). The paper describes the accident and gives brief characteristics of the efficacy of the implemented protective measures that made it possible to considerably reduce doses to the exposed population. The paper also provides retrospective dosimetry estimates for the members of the EURT Cohort (EURTC) which comprises approximately 21 400 people. During the first two years after the accident a decrease in the group average leukocyte (mainly due to neutrophils and lymphocytes) and thrombocyte count was observed in the population. At later dates an increased excess relative risk of solid cancer incidence and mortality was found in the EURTC.

Cancer Incidence after In Utero Exposure to Ionizing Radiation in Techa River Residents.

Health effects of in utero exposure to ionizing radiation, especially among adults, are still unclear. The aim of this study was to analyze cancer risk in a cohort of subjects exposed in utero due to releases of nuclear waste into the Techa River in the Southern Urals, taking into account additional postnatal exposure. Analysis for solid cancer was based on 242 cases among 10,482 cohort members, accumulating 381,948 person-years at risk, with follow-up from 1956-2009, while analysis for hematological malignancies was based on 26 cases among 11,070 persons, with 423,502 person-years at risk, with follow-up from 1953-2009. Mean doses accumulated in soft tissues and in red bone marrow during the prenatal period were 4 mGy and 30 mGy, respectively. Additional respective mean postnatal doses received by cohort members were 11 and 84 mGy. Poisson regression analysis was used to estimate the excess relative risk (ERR) of cancer incidence related to in utero and postnatal doses. No association was observed for in utero exposure with solid cancer risk [ERR per 10 mGy: -0.007; 95% confidence interval (CI): <-0.107; 0.148] or with hematological malignancy risk (ERR/10 mGy: -0.011; 95% CI: <-0.015; 0.099). However, ERR of solid cancer increased significantly with increasing postnatal dose (ERR/10 mGy: 0.11; 95% CI: 0.04; 0.22). The very wide confidence intervals in these ERR results are similar to those of studies performed on the LSS cohort and the offspring of the Mayak Female Worker Cohort, as well as case-control studies of effects after in utero medical exposure. There were limitations of this study, with decreased statistical power, due to the low prenatal doses received by most of the cohort members, the small number of cancer cases and the absence of cohort members over the age of 59 years (living cohort members had reached 49-59 years of age). Further aging of the cohort and extension of the follow-up period will enhance the statistical power of this study in the future. There is a shortage of cohort studies reporting on the effects of prenatal radiation exposure, as well as information on chronic exposure during the prenatal period. Therefore, further research of this unique cohort will be a useful addition to the published literature on this subject, and a valuable means of elucidating the long-term effects of low-dose radiation exposure in the fetus.

[Application of the EPR and FISH Methods to Dose Reconstruction for People Exposed in the Techa River Area].

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.

[Assessment of Erythropoiesis Status in Roach (Rutilus rutilus) of the Radioactively Contaminated Techa River].

At present volumetric activity of ß-emitting radionuclides in water at various locations of the Techa River ranges from 5 to 40-Bq/L; a specific activity of ß-emitting radionuclides in the bottom sediments at various locations ranges 10 Ito 106 Bq/kg dry weight. A significant increase of the erythroblast content in blood as compared to that in the roach from the reference watercourse (the Miass River) was observed during spawning in the spring. Due to this fact the number of erythrocytes was equal to that in the control animals under chronic radiation exposure at the dose rates of 0.9 and 16 µGy/day, and was insufficient at the dose rate of 108 gGy/day. During summer feeding no changes in the indexes of erythropoiesis in roach were observed under chronic radiation exposure at the dose rate of 0.9 µGy/day; the number of erythrocytes in the peripheral blood declines when the dose rates are 16 and 108 µGy/day. When performing a regression analysis, we revealed a dose-rate-dependent decrease in the absolute number of erythrocytes, normocytes, polychromatocytes, dividing and non-dividing erythroid cells in the peripheral blood of roach from the Techa River and an increase of a relative number of normochromatophylic erythrocytes.

NORMAL TISSUE REACTIONS TO CHRONIC RADIATION EXPOSURE IN MAN.

This paper presents an overview of radiobiological dependences governing the occurrence of tissue (organ) reactions that determine the outcomes of chronic exposure to low-LET ionizing radiation (IR) in humans. The mechanisms involved in the development of tissue reactions (TRs) to long-term exposures to IR and radioadaptation are considered. The overview describes the reactions of the haematopoietic, immune, nervous, reproductive and endocrine systems, lungs, skin and crystalline lens to chronic radiation exposure, which are of fundamental importance in view of radiation protection. It is shown that the individual's physiological tissue (organ) reserve, and also that induced by radiation exposure at low-dose rates are of great significance in the context of TR development.

[Apoptosis of Peripheral Blood Lymphocytes in the Members of the Techa River Cohort Chronically Exposed to Radiation].

The purpose of the present research was to estimate the intensity of the apoptotic death of lymphocytes during the period of carcinogenic effect realization in the residents of the Techa riverside villages. The investigation included analyses of the frequency of lymphocytes at the early and late stages of apoptosis and necrosis of peripheral blood lymphocytes using the method of FITC Annexin V, lymphocyte counts at the stage of DNA fragmentation using the TUNEL method, and the number of CD95(+)-lymphocytes. In the capacity of additional tests, loading tests involving in vitro irradiation at the dose of 1 Gy of a suspension of lymphocytes and incubations for 5 and 24 hours were used. Activation of the initial apoptotic and necrotic death of peripheral blood lymphocytes was revealed in the persons chronically exposed to low-intensity radiation within the range from 0.01 to 4.23 Gy. Exposed patients demonstrated a decrease in the number of CD95(+)-cells as compared to unexposed patients. The results of the cell death studies in the persons residing in the Techa riverside villages testify indirectly to the genomic instability of the peripheral blood lymphocytes.

Evaluation of distribution coefficients and concentration ratios of (90)Sr and (137)Cs in the Techa River and the Miass River.

Empirical data on the behavior of radionuclides in aquatic ecosystems are needed for radioecological modeling, which is commonly used for predicting transfer of radionuclides, estimating doses, and assessing possible adverse effects on species and communities. Preliminary studies of radioecological parameters including distribution coefficients and concentration ratios, for (90)Sr and (137)Cs were not in full agreement with the default values used in the ERICA Tool and the RESRAD BIOTA codes. The unique radiation situation in the Techa River, which was contaminated by long-lived radionuclides ((90)Sr and (137)Cs) in the middle of the last century allows improved knowledge about these parameters for river systems. Therefore, the study was focused on the evaluation of radioecological parameters (distribution coefficients and concentration ratios for (90)Sr and (137)Cs) for the Techa River and the Miass River, which is assumed as a comparison waterbody. To achieve the aim the current contamination of biotic and abiotic components of the river ecosystems was studied; distribution coefficients for (90)Sr and (137)Cs were calculated; concentration ratios of (90)Sr and (137)Cs for three fish species (roach, perch and pike), gastropods and filamentous algae were evaluated. Study results were then compared with default values available for use in the well-known computer codes ERICA Tool and RESRAD BIOTA (when site-specific data are not available). We show that the concentration ratios of (137)Cs in whole fish bodies depend on the predominant type of nutrition (carnivores and phytophagous). The results presented here are useful in the context of improving of tools for assessing concentrations of radionuclides in biota, which could rely on a wider range of ecosystem information compared with the process limited the current versions of ERICA and RESRAD codes. Further, the concentration ratios of (90)Sr are species-specific and strongly dependent on Ca(2+) concentration in water. The universal characteristic allows us to combine the data of fish caught in the water with different mineralization by multiplying the concentration of Ca(2+). The concentration ratios for fishes were well-fitted by Generalized Logistic Distribution function (GLD). In conclusion, the GLD can be used for probabilistic modeling of the concentration ratios in freshwater fishes to improve the confidence in the modeling results. This is important in the context of risk assessment and regulatory.

Characterization of biocenoses in the storage reservoirs of liquid radioactive wastes of Mayak PA. Initial descriptive report.

As a result of operation of the Mayak Production Association (Mayak PA), Chelyabinsk Oblast, Russia, an enterprise for production and separation of weapon-grade plutonium in the Soviet Union, ecosystems of a number of water bodies have been radioactively contaminated. The article presents information about the current state of ecosystems of 6 special industrial storage reservoirs of liquid radioactive waste from Mayak PA: reservoirs R-3, R-4, R-9, R-10, R-11 and R-17. At present the excess of the radionuclide content in the water of the studied reservoirs and comparison reservoirs (Shershnyovskoye and Beloyarskoye reservoirs) is 9 orders of magnitude for (90)Sr and (137)Cs, and 6 orders of magnitude for alpha-emitting radionuclides. According to the level of radioactive contamination, the reservoirs of the Mayak PA could be arranged in the ascending order as follows: R-11, R-10, R-4, R-3, R-17 and R-9. In 2007-2012 research of the status of the biocenoses of these reservoirs in terms of phytoplankton, zooplankton, bacterioplankton, zoobenthos, aquatic plants, ichthyofauna, avifauna parameters was performed. The conducted studies revealed decrease in species diversity in reservoirs with the highest levels of radioactive and chemical contamination. This article is an initial descriptive report on the status of the biocenoses of radioactively contaminated reservoirs of the Mayak PA, and is the first article in a series of publications devoted to the studies of the reaction of biocenoses of the fresh-water reservoirs of the Mayak PA to a combination of natural and man-made factors, including chronic radiation exposure.

Contemporary Understanding of Radioactive Contamination of the Techa River in 1949-1956.

Analysis of recently available archive materials regarding the liquid radioactive waste storage and reprocessing at the "Mayak" Production Association in 1949-1956 has led to a more accurate reconstruction of radionuclide releases into the Techa River. Radionuclide concentrations in the Techa River water, bottom sediments and floodplain soils in 1949-1951 were reconstructed with the use of a purposely-developed Techa River model. Model calculations agree with the measurements of the specific activity in the river water and bottom sediments conducted since 1951. The model output for the (90)Sr concentration in the river water shows a good agreement with the retrospective estimates derived from (90)Sr measurements in teeth and the whole body of the Techa riverside residents. Modeled (137)Cs-contamination of the floodplain shows agreement with the values reconstructed from (137)Cs measurements in the floodplain soils obtained in later years. Reconstructed contamination levels by radionuclides in the Techa River water and floodplain are being used to refine internal and external doses and risk estimates of late effects in the population chronically exposed to radiation.

[Cognitive impairments in persons exposed to radiation during the period of prenatal development].

OBJECTIVE: To assess the cognitive status in persons exposed to ionizing radiation in prenatal period. MATERIAL AND METHODS: The study included in-utero exposed people (n = 77), and the comparison group (n = 73), which consisted of people who lived in the territories of the Chelyabinsk Oblast that were not radioactive. The following methods were used: clinical, clinical-psychological (Mini-Mental State Examination (MMSE), the WAIS test, the proverb interpretation task, neurophysiological (EEG) methods, laboratory-based methods (cholesterol, high and low-density lipoproteins, triglycerides, cortisol, melatonin), and methods of statistical data processing. RESULTS AND CONCLUSION: The number of people with non-psychotic mental disorders with the prevalence of organic mental disorders (cognitive and asthenic) was significantly higher among in-utero exposed subjects. A neurophysiological study revealed more severe changes in the bioelectric brain activity with the presence of pathological and theta-rhythms in exposed persons. The clinical-psychological study revealed a significant decrease in the analytic/synthetic ability in exposed people and significantly lower level of the general and verbal IQ. These changes were accompanied by higher levels of cortisol and melatonin which led to the activation and tension of the adaptation mechanisms in in-utero exposed subjects.

Solid Cancer Incidence in the Techa River Incidence Cohort: 1956-2007.

Previously reported studies of the Techa River Cohort have established associations between radiation dose and the occurrence of solid cancers and leukemia (non-CLL) that appear to be linear in dose response. These analyses include 17,435 cohort members alive and not known to have had cancer prior to January 1, 1956 who lived in areas near the river or Chelyabinsk City at some time between 1956 and the end of 2007, utilized individualized dose estimates computed using the Techa River Dosimetry System 2009 and included five more years of follow-up. The median and mean dose estimates based on these doses are consistently higher than those based on earlier Techa River Dosimetry System 2000 dose estimates. This article includes new site-specific cancer risk estimates and risk estimates adjusted for available information on smoking. There is a statistically significant (P = 0.02) linear trend in the smoking-adjusted all-solid cancer incidence risks with an excess relative risk (ERR) after exposure to 100 mGy of 0.077 with a 95% confidence interval of 0.013-0.15. Examination of site-specific risks revealed statistically significant radiation dose effects only for cancers of the esophagus and uterus with an ERR per 100 mGy estimates in excess of 0.10. Esophageal cancer risk estimates were modified by ethnicity and sex, but not smoking. While the solid cancer rates are attenuated when esophageal cancer is removed (ERR = 0.063 per 100 mGy), a dose-response relationship is present and it remains likely that radiation exposure has increased the risks for most solid cancers in the cohort despite the lack of power to detect statistically significant risks for specific sites.

Methods for Ensuring High Quality of Coding of Cause of Death. The Mortality Register to Follow Southern Urals Populations Exposed to Radiation.

BACKGROUND: To follow up populations exposed to several radiation accidents in the Southern Urals, a cause-of-death registry was established at the Urals Center capturing deaths in the Chelyabinsk, Kurgan and Sverdlovsk region since 1950. OBJECTIVES: When registering deaths over such a long time period, quality measures need to be in place to maintain quality and reduce the impact of individual coders as well as quality changes in death certificates. METHODS: To ensure the uniformity of coding, a method for semi-automatic coding was developed, which is described here. Briefly, the method is based on a dynamic thesaurus, database-supported coding and parallel coding by two different individuals. RESULTS: A comparison of the proposed method for organizing the coding process with the common procedure of coding showed good agreement, with, at the end of the coding process, 70 - 90% agreement for the three-digit ICD -9 rubrics. CONCLUSIONS: The semi-automatic method ensures a sufficiently high quality of coding by at the same time providing an opportunity to reduce the labor intensity inherent in the creation of large-volume cause-of-death registries.