Effects of confounding and effect-modifying lifestyle, environmental and medical factors on risk of radiation-associated cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide. It has been known for some considerable time that radiation is associated with excess risk of CVD. A recent systematic review of radiation and CVD highlighted substantial inter-study heterogeneity in effect, possibly a result of confounding or modifications of radiation effect by non-radiation factors, in particular by the major lifestyle/environmental/medical risk factors and latent period. METHODS: We assessed effects of confounding by lifestyle/environmental/medical risk factors on radiation-associated CVD and investigated evidence for modifying effects of these variables on CVD radiation dose-response, using data assembled for a recent systematic review. RESULTS: There are 43 epidemiologic studies which are informative on effects of adjustment for confounding or risk modifying factors on radiation-associated CVD. Of these 22 were studies of groups exposed to substantial doses of medical radiation for therapy or diagnosis. The remaining 21 studies were of groups exposed at much lower levels of dose and/or dose rate. Only four studies suggest substantial effects of adjustment for lifestyle/environmental/medical risk factors on radiation risk of CVD; however, there were also substantial uncertainties in the estimates in all of these studies. There are fewer suggestions of effects that modify the radiation dose response; only two studies, both at lower levels of dose, report the most serious level of modifying effect. CONCLUSIONS: There are still large uncertainties about confounding factors or lifestyle/environmental/medical variables that may influence radiation-associated CVD, although indications are that there are not many studies in which there are substantial confounding effects of these risk factors.

Risk of central nervous system tumour incidence in a cohort of workers chronically exposed to ionising radiation.

The aim of the present study was to assess the risk of primary central nervous system (CNS) tumour incidence in a cohort of 22,377 Mayak Production Association workers chronically exposed to ionising radiation. There were 96 primary CNS tumours, including 42 cases of glioma and 44 cases of meningioma, registered during the whole follow-up period (1948-2018). The study demonstrated that the risk of primary CNS tumour incidence was associated with sex, attained age, calendar period, tall body height, age at the beginning of exposure, and facility type. There was no association found between risk of CNS tumour incidence and body mass index, smoking (males) and alcohol consumption status. The study did not find an effect of the total external gamma radiation dose absorbed in the brain on risk of CNS tumour incidence irrespective of whether an adjustment for the total external neutron dose absorbed in the brain was included or not. Excess relative risk per 1 Gy of external gamma brain dose was 0.05 (95% confidence interval (CI) -0.30; 0.70) for all CNS tumours, -0.18 (95% CI -; 0.44) for gliomas, and 0.38 (95% CI -0.32; 2.08) for meningiomas without adjustment for total neutron brain dose. There was no effect modification by sex, attained age, age at hire or facility.

Immunohistochemical Analysis of Lung Adenocarcinoma in Russian Mayak Nuclear Workers.

Specimens of lung adenocarcinoma (AdCa) from Russian nuclear workers (n = 54) exposed to alpha particles and gamma rays and from individuals non-exposed to radiation (n = 21) were examined using immunohistochemistry. Estimated significant associations with alpha dose were negative for Ki-67 and collagen IV in AdCa. Associations with gamma-ray dose were negative for tissue inhibitor of matrix metalloproteinase 2 and caspase 3 and positive for matrix metalloproteinase 2 and leukemia inhibiting factor in AdCa. The findings provide some evidence supporting alterations in apoptosis, cell proliferation and extracellular matrix in lung tissues affected by chronic radiation exposure that can contribute to radiogenic cancerogenesis.

Incidence risks for subtypes of heart diseases in a Russian cohort of Mayak Production Association nuclear workers.

Heart diseases are one of the main causes of death. The incidence risks were assessed for various types of heart diseases (HDs) in a cohort of Russian nuclear workers of the Mayak Production Association (PA) who had been chronically occupationally exposed to external gamma and/ or internal alpha radiation. The study cohort included all workers (22,377 individuals) who had been hired at the Mayak PA during 1948-1982 and followed up until 31 December 2018. The mean gamma-absorbed dose to the liver (standard deviation) was 0.43 (0.63) Gy, and the mean alpha-absorbed dose to the liver was 0.25 (1.19) Gy. Excess relative risk (ERR) per unit liver-absorbed dose (Gy) was calculated based on maximum likelihood. At the end of the follow-up, 559 chronic rheumatic heart disease (CRHD), 7722 ischemic heart disease (IHD) [including 2185 acute myocardial infarction (AMI) and 3976 angina pectoris (AP)], 4939 heart failure (HF), and 3689 cardiac arrhythmia and conduction disorder (CACD) cases were verified in the study cohort. Linear model fits of the gamma dose response for HDs were best once adjustments for non-radiation factors (sex, attained age, calendar period, smoking status and alcohol consumption) and alpha dose were included. ERR/Gy in males and females was 0.17 (95% confidence intervals: 0.10, 0.26) and 0.23 (0.09, 0.38) for IHD; 0.18 (0.09, 0.29) and 0.26 (0.08, 0.49) for AP; - 0.01 (n/a, 0.1) and - 0.01 (n/a, 0.27) for AMI; 0.27 (0.16, 0.40) and 0.27 (0.10, 0.49) for HF; 0.32 (0.19, 0.46) and 0.05 (- 0.09, 0.22) for CACD; 0.73 (- 0.02, 2.40) and - 0.12 (- 0.50, 0.69) for CRHD, respectively. Sensitivity analyses demonstrated the persistence of a significant dose-response regardless of exclusion/inclusion of adjustments for known potential non-radiation confounders (smoking, alcohol consumption, body mass index, hypertension, diabetes mellitus), and it was only the magnitude of the risk estimate that varied. The risks of HD incidence were not modified with sex (except for the CACD risk). This study provides evidence for a significant association of certain types of HDs with cumulative dose of occupational chronic external exposure to gamma radiation.

Incidence risks for cerebrovascular diseases and types of stroke in a cohort of Mayak PA workers.

Incidence risks for cerebrovascular diseases (CeVD) and some types of stroke in a cohort of 22,377 Russian Mayak nuclear workers chronically exposed to ionising radiation and followed up until the end of 2018 are reported. Among total 9469 cases of CeVD, 2078 cases were strokes that included 262 hemorrhagic strokes (HS) and 1611 ischemic strokes (IS). Data evaluation was performed with categorical and dose-response analyses estimating the relative risk (RR) and excess relative risk (ERR) per unit cumulative liver absorbed dose of external gamma-ray or internal alpha-particle exposure based on a linear model utilizing the AMFIT module of the EPICURE software. CeVD incidence was found to be significantly associated with cumulative radiation dose: ERR/Gy was 0.37 (95% confidence interval (CI) 0.27, 0.47) in males and 0.47 (95% CI 0.31, 0.66) in females for external exposure, and 0.31 (95% CI 0.11, 0.59) in males and 0.32 (95% CI 0.11, 0.61) in females for internal exposure. When the model for the analysis of external radiation effect did not include an adjustment for alpha radiation dose (and vice versa), the radiogenic risk estimate increased notably both for males and for females. In contrast, exclusion from or inclusion in the model of additional adjustments for non-radiation factors did not notably change the risk estimates. ERR/Gy of external gamma dose for CeVD incidence significantly decreased with increasing attained age (males and females) and duration of employment (females). No significant associations of either stroke or its types with cumulative gamma-ray dose of external exposure or alpha-particle dose of internal exposure were found.

Mortality from various diseases of the circulatory system in the Russian Mayak nuclear worker cohort: 1948-2018.

This paper reports on the findings from the study of mortality from diseases of the circulatory system (DCS) in Russian nuclear workers of the Mayak Production Association (22 377 individuals, 25.4% female) who were hired at the facility between 1948 and 1982 and followed up until the end of 2018. Using the AMFIT module of the EPICURE software, relative risks (RRs) and excess RRs per unit absorbed dose (ERR/Gy) for the entire Mayak cohort, the subcohort of workers who were residents of the dormitory town of Ozyorsk and the subcohort of migrants from Ozyorsk were calculated based on maximum likelihood. The mean cumulative liver absorbed gamma-ray dose from external exposure was 0.45 (0.65) Gy (mean (standard deviation)) for men and 0.37 (0.56) Gy for women. The mean cumulative liver absorbed alpha dose from internal exposure to incorporated plutonium was 0.18 (0.65) Gy for men and 0.40 (1.92) Gy for women. By the end of the follow-up, 6019 deaths with DCS as the main cause of death were registered among Mayak Production Association workers (including 3828 deaths in the subcohort of residents and 2191 deaths in the subcohort of migrants) over 890 132 (622 199/267 933) person-years of follow-up. The linear model that took into account non-radiation factors (sex, attained age, calendar period, smoking status and alcohol drinking status) and alpha radiation dose (via adjusting) did not demonstrate significant associations of mortality from DCS, ischaemic heart disease (IHD) and cerebrovascular disease with gamma-ray exposure dose in the entire cohort, the resident subcohort or the migrant subcohort (either in men or women). For the subcohort of residents, a significant association with gamma dose was observed for mortality from ischaemic stroke in men with ERR/Gy = 0.43 (95% CI 0.08; 0.99); there were no significant associations with liver absorbed gamma dose for any other considered outcomes. As for internal exposure, for men no significant associations of mortality from any DCS with liver absorbed alpha dose were observed, but for women positive associations were found for mortality from DCS (the entire cohort and the resident subcohort) and IHD (the entire cohort). No significant associations of mortality from various types of DCS with neutron dose were observed either in men or women, although neutron absorbed doses were recorded in only 18% of the workers.

Risk of skin cancer by histological type in a cohort of workers chronically exposed to ionizing radiation.

The incidence risk of non-melanoma skin cancer (NMSC), in particular basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), was investigated in a cohort of workers of the Russian nuclear facility, the Mayak Production Association (PA), who had been occupationally exposed to low dose-rate ionizing radiation over prolonged periods. The study cohort included all workers who had been hired at the enterprise in 1948-1982 and followed up to 31.12.2018 (22,377 individuals, 25% of females). The mean cumulative skin absorbed dose of external gamma-ray exposure was 0.50 ± 0.73 Gy (the range of 0.00-8.84 Gy); the mean cumulative skin absorbed dose of neutron exposure was 0.002 ± 0.004 Gy (the range of 0.0000002-0.153 Gy). Relative risk and excess relative risk per unit skin absorbed dose of external exposure (RR and ERR/Gy) were estimated using AMFIT module of EPICURE software. Over the entire follow-up period 295 (84.8%) BCC, 48 (13.8%) SCC and 5 (1.4%) skin appendage cell carcinomas (SACC) were registered among NMSC in members of the study cohort. A significant linear association of the BCC incidence with the cumulative skin absorbed dose of external gamma-ray exposure was observed: ERR/Gy = 0.57 (95% CI 0.24, 1.06). Inclusion of an adjustment for neutron dose in the model resulted in a modest reduction of the BCC risk estimate [ERR/Gy = 0.55 (95% CI 0.23, 1.03)]. No significant association was revealed for SCC incidence with cumulative skin absorbed dose of external gamma-ray exposure [ERR/Gy = 0.14 (95% CI - 0.23, 0.91)]; inclusion of the neutron dose adjustment in the model did not modify the estimated SCC risk. No modification of the BCC and SCC incidence risks by sex, age at hire, attained age and facility type was observed.

On the choice of methodology for evaluating dose-rate effects on radiation-related cancer risks.

Recently, several compilations of individual radiation epidemiology study results have aimed to obtain direct evidence on the magnitudes of dose-rate effects on radiation-related cancer risks. These compilations have relied on meta-analyses of ratios of risks from low dose-rate studies and matched risks from the solid cancer Excess Relative Risk models fitted to the acutely exposed Japanese A-bomb cohort. The purpose here is to demonstrate how choices of methodology for evaluating dose-rate effects on radiation-related cancer risks may influence the results reported for dose-rate effects. The current analysis is intended to address methodological issues and does not imply that the authors recommend a particular value for the dose and dose-rate effectiveness factor. A set of 22 results from one recent published study has been adopted here as a test set of data for applying the many different methods described here, that nearly all produced highly consistent results. Some recently voiced concerns, involving the recalling of the well-known theoretical point-the ratio of two normal random variables has a theoretically unbounded variance-that could potentially cause issues, are shown to be unfounded when aimed at the published work cited and examined in detail here. In the calculation of dose-rate effects for radiation protection purposes, it is recommended that meta-estimators should retain the full epidemiological and dosimetric matching information between the risks from the individual low dose-rate studies and the acutely exposed A-bomb cohort and that a regression approach can be considered as a useful alternative to current approaches.

Risk of cataract removal surgery in Mayak PA workers occupationally exposed to ionizing radiation over prolonged periods.

In this study, the risk of cataract removal surgery was assessed in a cohort of workers occupationally exposed to ionizing radiation over a prolonged period. The study cohort includes 22,377 workers of the Mayak Production Association (about 25% of whom are females) first employed at one of the main facilities in 1948-1982, who were followed up to the end of 2008. Dose estimates used in the study are provided by the Mayak Worker Dosimetry System 2008. The mean cumulative dose from external γ-rays [personal dose equivalent Hp(10)] is 0.54 ± 0.76 Sv for males and 0.44 ± 0.65 Sv for females. The mean cumulative doses from neutrons (personal dose equivalent Hp(10)n) were 0.034 ± 0.080 Sv for males and 0.033 ± 0.092 Sv for females. Relative risks and excess relative risks per unit dose were calculated based on maximum likelihood. Among 4,177 workers diagnosed with a verified diagnosis of senile cataract, 701 lens removal surgeries (16.7%) were performed by the end of the follow-up period. The risk of cataract removal surgery was shown to be significantly associated with non-radiation factors such as sex, attained age, smoking, an ocular comorbidity (e.g., glaucoma), and a somatic comorbidity (e.g., diabetes mellitus). There was no significant association of cataract removal surgery with external γ-dose regardless of inclusion of the neutron dose adjustment with either linear or non-linear models. It is concluded that cataract removal surgery rate may not be a highly sensitive and specific indicator that could serve as a surrogate for radiation-related cataracts.

Registry for chronic radiation syndrome in a worker cohort of the Russian nuclear enterprise, Mayak Production Association.

A registry for chronic radiation syndrome (CRS), a deterministic effect of chronic exposure to external and/or internal radiation at doses and dose rates exceeding thresholds for tissue reactions, was established within a medical and dosimetry database known as 'Clinics', of the Southern Urals Biophysics Institute at the Federal Medical and Biological Agency of Russia. It includes 2068 CRS cases: 1517 (73.4%) in males and 551 (26.6%) in females. The majority of workers (97.9%) diagnosed with CRS at one of the main facilities of the first Russian nuclear enterprise, Mayak Production Association, were hired in the period 1948-1954. On the date of CRS diagnosis, the mean cumulative red bone marrow (RBM) absorbed doses from external gamma rays were 1.1 ± 0.66 Gy in males and 1.0 ± 0.58 Gy (±standard deviation) in females, with mean annual doses of 0.46 ± 0.33 Gy and 0.38 ± 0.22 Gy, respectively, and maximum annual doses of 0.67 ± 0.46 Gy and 0.55 ± 0.34 Gy, respectively. The frequency of CRS cases significantly increased with the increasing cumulative and mean annual RBM absorbed doses from external gamma rays. The paper presents the structure and descriptive characteristics of the CRS registry as well as prospects for its use.

Risk of various types of cataracts in a cohort of Mayak workers following chronic occupational exposure to ionizing radiation.

This study is the first to report cataract type specific risks in a cohort of Russian Mayak Production Association workers following chronic occupational exposure to ionizing radiation. In this retrospective cohort study, 22,377 workers (females 25.4%) first employed in 1948-1982 were followed up till the end of 2008. All cataract subtypes were significantly dependent on sex, attained age, diabetes mellitus, myopia and glaucoma. For each of posterior subcapsular (PSC), cortical and nuclear cataracts, the risk of cataract incidence significantly linearly increased with increasing radiation dose. Excess relative risk per unit effective dose (ERR/Sv) from external γ-rays based on the linear model was 0.91 [95% confidence intervals (CIs) 0.67, 1.20] for PSC, 0.63 (95% CIs 0.49, 0.76) for cortical, and 0.47 (95% CIs 0.35, 0.60) for nuclear cataracts. For all three types of cataracts, exclusion of an adjustment for neutron dose as well as inclusion of additional adjustments for body mass index and smoking index decreased ERR/Sv of external γ-rays. Inclusion of an additional adjustment for glaucoma, however, modestly increased incidence risks for cortical and nuclear cataracts, but not PSC cataracts. Inclusion of an adjustment for diabetes mellitus decreased ERR/Sv of external γ-rays only for PSC incidence. Both males and females had increased risks for all three types of cataracts, but ERR/Sv was significantly higher in females than in males (p < 0.001), particularly for PSC cataracts. The results suggest that chronic occupational radiation exposure significantly increases risks of PSC, cortical and nuclear cataracts, and that such risks are higher in females than in males.

Risk of lower extremity arterial disease in a cohort of workers occupationally exposed to ionizing radiation over a prolonged period.

In this study the incidence risk of lower extremity arterial disease (LEAD; international classification of diseases version 9 code 440.2) was assessed in a cohort of workers occupationally exposed to radiation over a prolonged period. The study cohort includes 22,377 workers of the Mayak Production Association (25% of whom are females) first employed at one of the main facilities in 1948-1982 and followed up to the end of 2008. Dose estimates used in the study are provided by Mayak Worker Dosimetry System 2008. The mean total dose from external gamma-rays is 0.54 Gy for males and 0.44 Gy for females. The mean absorbed liver dose from internal alpha-radiation due to incorporated plutonium is 0.23 Gy in males and 0.44 Gy in females. Relative risks and excess relative risks per unit dose (ERR/Gy) are calculated based on maximum likelihood. A total of 943 cases of LEAD are registered in the study cohort during the follow-up of 512,801 person-years. A significant association of LEAD incidence with total dose from external gamma-rays (based on a linear model) was revealed, and the ERR/Gy is 0.27 (95% confidence interval (CI) 0.11; 0.48). It turned out that a linear-exponential model provides a better fit of the data (∆AIC = 9.957). Inclusion of an adjustment for internal alpha-radiation dose resulted in the reduction of the ERR/Gy to 0.19 (95% CI 0.05; 0.39), but the risk remains significant. No association of LEAD incidence with dose from internal alpha-radiation was found in the study worker cohort. It is concluded that this study provides evidence for an association of LEAD incidence with dose from external gamma-rays taking non-radiation factors into account.

Mortality of populations potentially exposed to ionising radiation, 1953-2010, in the closed city of Ozyorsk, Southern Urals: a descriptive study.

BACKGROUND: The city of Ozyorsk (Southern Urals) was created as a secret city in 1945 and is a closed city until today. It housed workers of the earliest and one of the country's largest nuclear facilities. Workers of the nuclear reactors, radiochemical or reprocessing plants were exposed to high levels of ionising radiation in the early years of operation and possibly further exposed from inhalation of plutonium aerosols. METHODS: The cause-of-death registry of Ozyorsk received paper copies of original death certificates of all deaths of residents of the city. Data were analysed for recent mortality rates (1998-2010) and time trends in age-standardised mortality rates between 1953 and 2010 of main groups of causes of deaths, in particular cancer. RESULTS: Comparing workers of the three main plant types with the remainder of the Ozyorsk residents, and with national figures, all-cause mortality rates were lowest among workers, with ratios compared to national figures of 0.65 (men) and 0.56 (women), and compared to the other residents of 0.77 (men) and of 0.74 (women). For cancer overall, the differences were smaller in men (ratio between workers and national figures of 0.86) and there were no differences in women (ratio of 1.00), but ratios differed by cancer type. Most cancer deaths were however least common in the workers, including leukaemia. Over the last 60 years, all-cause mortality has gradually increased among men in all three groups but was stable among women, whereas cancer death rates have slightly declined in both sexes. CONCLUSIONS: Healthy worker effect, relatively better living conditions in Ozyorsk and healthier lifestyles may explain the lower mortality rates in Ozyorsk. Overall mortality time trends in Ozyorsk were similar to the entire country. No apparent radiation-related effects were seen in this population-level analysis, but the radiation-related risks can be better addressed in individual-level studies.

Chromosome aberrations in workers with exposure to α-particle radiation from internal deposits of plutonium: expectations from in vitro studies and comparisons with workers with predominantly external γ-radiation exposure.

mFISH analysis of chromosome aberration profiles of 47 and 144 h lymphocyte cultures following exposure to 193 mGy α-particle radiation confirmed that the frequency of stable aberrant cells and stable cells carrying translocations remains constant through repeated cell divisions. Age-specific rates and in vitro dose-response curves were used to derive expected translocation yields in nine workers from the Mayak nuclear facility in Russia. Five had external exposure to γ-radiation, two of whom also had exposure to neutrons, and four had external exposure to γ-radiation and internal exposure to α-particle radiation from incorporated plutonium. Doubts over the appropriateness of the dose response used to estimate translocations from the neutron component made interpretation difficult in two of the workers with external exposure, but the other three had translocation yields broadly in line with expectations. Three of the four plutonium workers had translocation yields in line with expectations, thus supporting the application of the recently derived in vitro α-particle dose response for translocations in stable cells. Overall this report demonstrates that with adequate reference in vitro dose-response curves, translocation yield has the potential to be a useful tool in the validation of red bone marrow doses resulting from mixed exposure to external and internal radiation.

Verification by the FISH translocation assay of historic doses to Mayak workers from external gamma radiation.

The aim of this study was to apply the fluorescence in situ hybridization (FISH) translocation assay in combination with chromosome painting of peripheral blood lymphocytes for retrospective biological dosimetry of Mayak nuclear power plant workers exposed chronically to external gamma radiation. These data were compared with physical dose estimates based on monitoring with badge dosimeters throughout each person's working life. Chromosome translocation yields for 94 workers of the Mayak production association were measured in three laboratories: Southern Urals Biophysics Institute, Leiden University Medical Center and the former Health Protection Agency of the UK (hereinafter Public Health England). The results of the study demonstrated that the FISH-based translocation assay in workers with prolonged (chronic) occupational gamma-ray exposure was a reliable biological dosimeter even many years after radiation exposure. Cytogenetic estimates of red bone marrow doses from external gamma rays were reasonably consistent with dose measurements based on film badge readings successfully validated in dosimetry system "Doses-2005" by FISH, within the bounds of the associated uncertainties.

Dose and dose-rate effects of ionizing radiation: a discussion in the light of radiological protection.

The biological effects on humans of low-dose and low-dose-rate exposures to ionizing radiation have always been of major interest. The most recent concept as suggested by the International Commission on Radiological Protection (ICRP) is to extrapolate existing epidemiological data at high doses and dose rates down to low doses and low dose rates relevant to radiological protection, using the so-called dose and dose-rate effectiveness factor (DDREF). The present paper summarizes what was presented and discussed by experts from ICRP and Japan at a dedicated workshop on this topic held in May 2015 in Kyoto, Japan. This paper describes the historical development of the DDREF concept in light of emerging scientific evidence on dose and dose-rate effects, summarizes the conclusions recently drawn by a number of international organizations (e.g., BEIR VII, ICRP, SSK, UNSCEAR, and WHO), mentions current scientific efforts to obtain more data on low-dose and low-dose-rate effects at molecular, cellular, animal and human levels, and discusses future options that could be useful to improve and optimize the DDREF concept for the purpose of radiological protection.

Risks of circulatory diseases among Mayak PA workers with radiation doses estimated using the improved Mayak Worker Dosimetry System 2008.

The new Mayak Worker Dosimetry System 2008 (MWDS-2008) was published in 2013 and supersedes the Doses-2005 dosimetry system for Mayak Production Association (PA) workers. It provides revised external and internal dose estimates based on the updated occupational history data. Using MWDS-2008, a cohort of 18,856 workers first employed at one of the main Mayak PA plants during 1948-1972 and followed up to 2005 was identified. Incidence and mortality risks from ischemic heart disease (IHD) (International Classification of Diseases (ICD)-9 codes 410-414) and from cerebrovascular diseases (CVD) (ICD-9 codes 430-438) were examined in this cohort and compared with previously published risk estimates in the same cohort based on the Doses-2005 dosimetry system. Significant associations were observed between doses from external gamma-rays and IHD and CVD incidence and also between internal doses from alpha-radiation and IHD mortality and CVD incidence. The estimates of excess relative risk (ERR)/Gy were consistent with those estimates from the previous studies based on Doses-2005 system apart from the relationship between CVD incidence and internal liver dose where the ERR/Gy based on MWDS-2008 was just over three times higher than the corresponding estimate based on Doses-2005 system. Adjustment for smoking status did not show any effect on the estimates of risk from internal alpha-particle exposure.

mFISH analysis of chromosome aberrations in workers occupationally exposed to mixed radiation.

We performed a study on the presence of chromosome aberrations in a cohort of plutonium workers of the Mayak production association (PA) with a mean age of 73.3 ± 7.2 years to see whether by multi-color fluorescence in situ hybridization (mFISH) translocation analysis can discriminate individuals who underwent occupational exposure with internal and/or external exposure to ionizing radiation 40 years ago. All Mayak PA workers were occupationally exposed to chronic internal alpha-radiation due to incorporated plutonium-239 and/or to external gamma-rays. First, we obtained the translocation yield in control individuals by mFISH to chromosome spreads of age-matched individuals and obtained background values that are similar to previously published values of an international study (Sigurdson et al. in Mutat Res 652:112-121, 2008). Workers who had absorbed a total dose of >0.5 Gy external gamma-rays to the red bone marrow (RBM) displayed a significantly higher frequency of stable chromosome aberrations relative to a group of workers exposed to <0.5 Gy gamma-rays total absorbed RBM dose. Thus, the translocation frequency may be considered to be a biological marker of external radiation exposure even years after the exposure. In a group of workers who were internally exposed and had incorporated plutonium-239 at a body burden >1.48 kBq, mFISH revealed a considerable number of cells with complex chromosomal rearrangements. Linear associations were observed for translocation yield with the absorbed RBM dose from external gamma-rays as well as for complex chromosomal rearrangements with the plutonium-239 body burden.

Expression of blood serum proteins and lymphocyte differentiation clusters after chronic occupational exposure to ionizing radiation.

This study aimed to assess effects of chronic occupational exposure on immune status in Mayak workers chronically exposed to ionizing radiation (IR). The study cohort consists of 77 workers occupationally exposed to external gamma-rays at total dose from 0.5 to 3.0 Gy (14 individuals) and workers with combined exposure (external gamma-rays at total dose range 0.7-5.1 Gy and internal alpha-radiation from incorporated plutonium with a body burden of 0.3-16.4 kBq). The control group consists of 43 age- and sex-matched individuals who never were exposed to IR, never involved in any cleanup operations following radiation accidents and never resided at contaminated areas. Enzyme-linked immunoassay and flow cytometry were used to determine the relative concentration of lymphocytes and proteins. The concentrations of T-lymphocytes, interleukin-8 and immunoglobulins G were decreased in external gamma-exposed workers relative to control. Relative concentrations of NKT-lymphocytes, concentrations of transforming growth factor-ß, interferon gamma, immunoglobulins A, immunoglobulins M and matrix proteinase-9 were higher in this group as compared with control. Relative concentrations of T-lymphocytes and concentration of interleukin-8 were decreased, while both the relative and absolute concentration of natural killers, concentration of immunoglobulins A and M and matrix proteinase-9 were increased in workers with combined exposure as compared to control. An inverse linear relation was revealed between absolute concentration of T-lymphocytes, relative and absolute concentration of T-helpers cells, concentration of interferon gamma and total absorbed dose from external gamma-rays in exposed workers. For workers with incorporated plutonium, there was an inverse linear relation of absolute concentration of T-helpers as well as direct linear relation of relative concentration of NKT-lymphocytes to total absorbed red bone marrow dose from internal alpha-radiation. In all, chronic occupational IR exposure of workers induced a depletion of immune cells in peripheral blood of the individuals involved.