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Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: Fission-2009-3.1.2 | Award Amount: 9.07M | Year: 2010

This project aims to improve estimates of the risks of long-term health effects associated with protracted external and internal radiation exposures, through further studies of exposed populations in the Southern Urals (Russian Federation). Specific objectives of the project are as follows: 1. To develop improved modules for estimating external doses to exposed cohorts in the Southern Urals. It is anticipated that new dosimetry systems that come into use after the end of SOLO will incorporate these modules and support future epidemiological work. 2. To carry out epidemiological studies of morbidity and mortality from non-cancer diseases - specifically respiratory and circulatory diseases - and of cancer incidence among workers at Mayak Production Association, based on Mayak-Doses-2008. 3. To examine the feasibility of conducting a pooled epidemiological analysis of the Mayak and Sellafield plutonium worker cohorts. A common internal dosimetry protocol for assessing doses from plutonium exposures will be produced , with quantification of uncertainties. If judged feasible, doses will be calculated and an epidemiological analysis undertaken. 4. To analyse the feasibility of conducting a pooled analysis of cancer incidence and mortality following in utero irradiation among the offspring of Mayak female workers and of the Techa River female population, based on the estimation of doses to the embryo and fetus, and - if judged feasible - to undertake this analysis. The research will be coordinated with related research in the Southern Urals. The findings should provide a more robust scientific basis for underpinning radiation protection standards.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: Fission-2011-3.1.1 | Award Amount: 5.49M | Year: 2011

Epidemiological evidence has established a link between cardiovascular disease and exposure of the heart and major vessels to doses above 500mGy. At lower doses the evidence for a detrimental effect is inconclusive. In part, this is due to the lack of appropriate epidemiological studies, coupled with lack of knowledge of the processes involved that is needed for construction of mathematical models. The ProCardio consortium will study cardiovascular outcomes in childhood cancer survivors where the radiation doses given to the heart are available. These data will be interrogated using new mathematical models developed from the data from our molecular and biological studies. These will use state-of-the-art technologies to map cardiovascular changes after photon irradiation at both low doses and low dose rates. This will be complemented by comparative studies using high LET irradiation. We will apply an integrative approach to combine transcriptional (mRNA and miRNA) and translational (proteomics) studies to understand the disease processes. High throughput proteomics (ICPL, SILAC and label-free analysis) will be used to identify new biomarkers of radiation-induced cardiovascular disease for future molecular epidemiological studies. These will be validated using the archives of cardiovascular tissue samples from the Mayak facility.


Recent epidemiological studies suggest that cancer risk after exposures with doses comparable to the dose limits for occupationally exposed workers may be larger than assumed by ICRP in the derivation of these limits. The value of cancer risk from such exposures and its dependence on tissue, radiation type and individual factors is largely unknown. The innovative approach proposed here combines epidemiology and radiobiology in order to quantify cancer risks after low-dose or low-dose-rate exposures to ionizing radiation. Key factors of radiation induced carcinogenesis such as genomic instability will be measured in cancer tissues and blood samples from members of the following radio-epidemiological cohorts: French Haemangioma Cohort, Mayak Worker Cohort and thyroid cancer cases after the Chernobyl accident. Inter-cellular communication after exposure to low-dose radiation exposure and its influence on apoptosis, cell proliferation, differentiation and genomic instability will be explored with 2D cell cultures and 3D tissue models. This includes research on stem cells, which will be isolated from healthy human breast tissue. The results of the radiobiological studies will be integrated in the development of models of carcinogenesis for evaluation of major epidemiological cohorts: Atomic Bomb Survivors, French-Swedish-Italian Thyroid Cancer Cohort, Mayak Worker Cohort, Swedish Haemangioma Cohort, UkrAm Cohort on thyroid cancer after the Chernobyl accident, and UK National Registry for Radiation Workers. Cancer risk will be determined for the breast, lung, thyroid and the digestive tract after low-dose-rate exposure to low-LET radiation (external gamma radiation and internal radiation from 131I) and to high-LET radiation (alpha-particles from incorporated plutonium). Lifetime cancer risks including individual risk factors will be calculated to establish a new basis for deriving dose limits and estimating cancer risks including those from medical diagnostic exposures.


Gilbert E.S.,U.S. National Cancer Institute | Sokolnikov M.E.,Southern Urals Biophysics Institute | Preston D.L.,HiroSoft International Corporation | Schonfeld S.J.,U.S. National Cancer Institute | And 3 more authors.
Radiation Research | Year: 2013

Workers at the Mayak nuclear facility in the Russian Federation offer a unique opportunity to evaluate health risks from exposure to inhaled plutonium. Risks of mortality from lung cancer, the most serious carcinogenic effect of plutonium, were evaluated in 14,621 Mayak workers who were hired in the period from 1948-1982, followed for at least 5 years, and either monitored for plutonium or never worked with plutonium. Over the follow-up period from 1953-2008, there were 486 deaths from lung cancer, 446 of them in men. In analyses that were adjusted for external radiation dose and smoking, the plutonium excess relative risk (ERR) per Gy declined with attained age and was higher for females than for males. The ERR per Gy for males at age 60 was 7.4 (95% CI: 5.0-11) while that for females was 24 (95% CI: 11-56). When analyses were restricted to plutonium doses <0.2 Gy, the ERR per Gy for males at age 60 was similar: 7.0 (95% CI: 2.5-13). Of the 486 lung cancer deaths, 105 (22%) were attributed to plutonium exposure and 29 (6%) to external exposure. Analyses of the 12,708 workers with information on smoking indicated that the relationship of plutonium exposure and smoking was likely sub-multiplicative (P = 0.011) and strongly indicated that it was super-Additive (P < 0.001). Although extensive efforts have been made to improve plutonium dose estimates in this cohort, they are nevertheless subject to large uncertainties. Large bioassay measurement errors alone are likely to have resulted in serious underestimation of risks, whereas other sources of uncertainty may have biased results in ways that are difficult to predict. © 2013 by Radiation Research Society.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: Fission-2008-3.1.1 | Award Amount: 1.31M | Year: 2009

The sharing of data and biomaterials from publicly funded experimental radiation science adds enormous value to the original investment. Sharing will yield substantial scientific rewards through re-analysis and new investigations. The goal of STORE is to generate a platform that will allow the storage and retrieval of both data and the corresponding biological material from past, current and future radiobiological studies. The STORE project will perform four tasks: 1) Deliver a Data Warehouse that will also present a single portal to radiobiological information distributed over scientific centres throughout the world. 2) Provide a foundation for the creation of a virtual store of biological material. 3) Establish Standard Operating Procedures (SOPs) on how best to evaluate, store and use the biological material to ensure that the collection, archiving and storage of these non-renewable materials are state-of-the-art. 4) Assess potential financial models for long term support of a bioresource and Data Warehouse for radiobiology. STORE will thus provide a mechanism for ensuring the future survival of these invaluable and irreplaceable resources and provide a platform for the sharing of new data across the radiobiology community


Wieser A.,Helmholtz Center for Environmental Research | Vasilenko E.,Southern Urals Biophysics Institute | Aladova E.,Southern Urals Biophysics Institute | Fattibene P.,Instituto Superiore Of Sanita | And 2 more authors.
Radiation and Environmental Biophysics | Year: 2014

In 1945, within the frame of the Uranium Project for the production of nuclear weapons, the Mayak nuclear facilities were constructed at the Lake Irtyash in the Southern Urals, Russia. The nuclear workers of the Mayak Production Association (MPA), who lived in the city of Ozyorsk, are the focus of epidemiological studies for the assessment of health risks due to protracted exposure to ionising radiation. Electron paramagnetic resonance measurements of absorbed dose in tooth enamel have already been used in the past, in an effort to validate occupational external doses that were evaluated in the Mayak Worker Dosimetry System. In the present study, 229 teeth of Ozyorsk citizens not employed at MPA were investigated for the assessment of external background exposure in Ozyorsk. The annually absorbed dose in tooth enamel from natural background radiation was estimated to be (0.7 ± 0.3) mGy. For citizens living in Ozyorsk during the time of routine noble gas releases of the MPA, which peaked in 1953, the average excess absorbed dose in enamel above natural background was (36 ± 29) mGy, which is consistent with the gamma dose obtained by model calculations. In addition, there were indications of possible accidental gaseous MPA releases that affected the population of Ozyorsk, during the early and late MPA operation periods, before 1951 and after 1960. © The Author(s) 2014.


Azizova T.V.,Southern Urals Biophysics Institute | Haylock R.G.E.,Public Health England | Moseeva M.B.,Southern Urals Biophysics Institute | Bannikova M.V.,Southern Urals Biophysics Institute | Grigoryeva E.S.,Southern Urals Biophysics Institute
Radiation Research | Year: 2014

Incidence and mortality from cerebrovascular disease (CVD) [International Classification of Diseases 9th revision (ICD-9) codes: 430-438] was studied in a cohort of 22,377 workers first employed at the Mayak Production Association (Mayak PA) in 1948-1982 and followed up to the end of 2008. The cohort size was increased by 19% and follow-up extended by 3 years over the previous analysis. Radiation doses were estimated using an updated dosimetry system: Mayak Worker Dosimetry System 2008 (MWDS-2008). For the first time, in an analysis of this cohort, quantitative smoking data were used. Workers of the study cohort were exposed occupationally to prolonged external gamma rays and internal alpha particles. The mean (±standard deviation) total dose from external gamma rays was 0.54 ± 0.76 Gy (95% percentile 2.21 Gy) for males and 0.44 ± 0.65 Gy (95% percentile 1.87 Gy) for females. The mean plutonium body burden in the 31% of workers monitored for internal exposure was 1.32 ± 4.87 kBq (95% percentile 4.71 kBq) for males and 2.21 ± 13.24 kBq (95% percentile 4.56 kBq) for females. The mean total absorbed alpha-particles dose to the liver from incorporated plutonium was 0.23 ± 0.77 Gy (95% percentile 0.89 Gy) in males and 0.44 ± 2.11 Gy (95% percentile 1.25 Gy) in females. After adjusting for nonradiation factors (gender, age, calendar period, employment period, facility, smoking, alcohol consumption), there were significantly increasing trends in CVD incidence associated with total absorbed dose from external gamma rays and total absorbed dose to the liver from internal alpha-particle radiation exposure. Excess relative risks per Gy (ERR/Gy) were 0.46 (95% CI 0.37, 0.57) and 0.28 (95% CI 0.16, 0.42), respectively, based on a linear dose-response model. Adjustments for additional factors (hypertension, body mass index, duration of employment, smoking index and total absorbed dose to the liver from internal exposure during the analysis of external exposure and vice versa) had little effect on the results. The categorical analyses showed that CVD incidence was significantly higher among workers with total absorbed external gamma-ray doses greater than 0.1 Gy compared to those exposed to lower doses and that CVD incidence was also significantly higher among workers with total absorbed internal alpha-particle doses to the liver from incorporated plutonium greater than 0.01 Gy compared to those exposed to lower doses. The results of the categorical analyses of CVD incidence were in good agreement with a linear dose response for external gamma-ray doses but for internal alpha-particle doses the picture was less clear. For the first time an excess risk of CVD mortality was seen in workers whose livers were exposed to internal alpha-particle doses greater than 0.1 Gy compared to those workers who were exposed to doses of less than 0.01 Gy. A significant increasing trend for CVD mortality with internal alpha-particle dose was revealed in the subcohort of workers exposed at doses <1.0 Gy after having adjusted for nonradiation factors, ERR/Gy = 0.84 (95% CI, 0.09, 1.92). These updated results provide good evidence for a linear trend in risk of CVD incidence with external gamma-ray dose. The trend for CVD incidence with internal alpha-particle dose is less clear due to the impact of issues concerning the use of dose estimates based on below the limit of detection bioassay measurements. © 2014 by Radiation Research Society.


Vostrotin V.V.,Southern Urals Biophysics Institute | Fell T.P.,Public Health England | Smith T.J.,Public Health England | Romanov S..,Southern Urals Biophysics Institute
International Journal of Radiation Biology | Year: 2014

Purpose: The estimation of plutonium fetal transfer and the calculation of individual in utero and postnatal doses for the Mayak Production Association (PA) offspring cohort. Materials and methods: The model developed by the International Commission on Radiological Protection (ICRP) for the transfer of plutonium to the fetus following maternal intakes before and during pregnancy has been adjusted for application to analysis of the fetal transfer of 239Pu for Mayak workers. Improved estimates of fetal to maternal concentration ratios (CF:CM) have been obtained based on a correlation observed between adult offsprings' measured daily urine 239Pu activity and estimates of their mothers' systemic activity at conception. Data on 239Pu activity in daily urine samples were collected from 13 selected adults whose mothers worked at the Mayak PA facility during the period from 1948-1953, before and/or during pregnancy. Results: A comparison of measured and modeled excretion data enabled a mean value of 0.18 ± 0.02 (n = 21) to be inferred for the Pu CF:CM ratio, with a coefficient of variation of 60%. Conclusions: Point estimates of the individual in utero and postnatal absorbed doses for the red bone marrow and liver were in the range 2...13 mGy in 95% of the cases for the cohort of 1936 offspring. © 2014 Informa UK, Ltd.


Zollner S.,Helmholtz Center Munich | Sokolnikov M.E.,Southern Urals Biophysics Institute | Eidemuller M.,Helmholtz Center Munich
PLoS ONE | Year: 2015

Mechanistic multi-stage models are used to analyze lung-cancer mortality after Plutonium exposure in the Mayak-workers cohort, with follow-up until 2008. Besides the established two-stage model with clonal expansion, models with three mutation stages as well as a model with two distinct pathways to cancer are studied. The results suggest that three-stage models offer an improved description of the data. The best-fitting models point to a mechanism where radiation increases the rate of clonal expansion. This is interpreted in terms of changes in cell-cycle control mediated by bystander signaling or repopulation following cell killing. No statistical evidence for a two-pathway model is found. To elucidate the implications of the different models for radiation risk, several exposure scenarios are studied. Models with a radiation effect at an early stage show a delayed response and a pronounced drop-off with older ages at exposure. Moreover, the dose-response relationship is strongly nonlinear for all three-stage models, revealing a marked increase above a critical dose. © 2015 Zöllner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Jacob P.,Helmholtz Center Munich | Meckbach R.,Helmholtz Center Munich | Kaiser J.C.,Helmholtz Center Munich | Sokolnikov M.,Southern Urals Biophysics Institute
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis | Year: 2010

Recent publications on the integration of radiobiological effects in the two-step clonal expansion (TSCE) model of carcinogenesis and applications to radioepidemiological data are reviewed and updated. First, a model version with radiation-induced genomic instability was shown to be a possible explanation for the age dependence of the radiation-induced cancer mortality in the Techa River Cohort. Second, it is demonstrated that inclusion of a bystander effect with a dose threshold allows an improved description of the lung cancer mortality risk for the Mayak workers cohort due to incorporation of plutonium. The threshold for the annual lung dose is estimated to 12 (90%CI: 4; 14). mGy/year. This threshold applies to the initiation of preneoplastic cells and to hyperplastic growth. There is, however, no evidence for a threshold for the effects of gamma radiation. Third, models with radiation-induced cell inactivation tend to predict lower cancer risks among the atomic bomb survivors with exposure at young age than conventionally used empirical models. Also, risks after exposures with doses in the order of 100. mGy are predicted to be higher in models with low-dose hypersensitivity than in models with conventional cell survival curves. In the reviewed literature, models of carcinogenesis tend to describe radioepidemiological data better than conventionally used empirical models. © 2010 Elsevier B.V.

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