Red Bone Marrow Dose Research Articles

Leukaemia, lymphoma, and multiple myeloma mortality after low-level exposure to ionising radiation in nuclear workers (INWORKS): updated findings from an international cohort study

A major update to the International Nuclear Workers Study (INWORKS) was undertaken to strengthen understanding of associations between low-dose exposure to penetrating forms of ionising radiation and mortality. Here, we report on associations between radiation dose and mortality due to haematological malignancies. We assembled a cohort of 309 932 radiation-monitored workers (269 487 [87%] males and 40 445 [13%] females) employed for at least 1 year by a nuclear facility in France (60 697 workers), the UK (147 872 workers), and the USA (101 363 workers). Workers were individually monitored for external radiation exposure and followed-up from Jan 1, 1944, to Dec 31, 2016, accruing 10·72 million person-years of follow-up. Radiation-mortality associations were quantified in terms of the excess relative rate (ERR) per Gy of radiation dose to red bone marrow for leukaemia excluding chronic lymphocytic leukaemia (CLL), as well as subtypes of leukaemia, myelodysplastic syndromes, non-Hodgkin and Hodgkin lymphomas, and multiple myeloma. Estimates of association were obtained using Poisson regression methods. The association between cumulative dose to red bone marrow, lagged 2 years, and leukaemia (excluding CLL) mortality was well described by a linear model (ERR per Gy 2·68, 90% CI 1·13 to 4·55, n=771) and was not modified by neutron exposure, internal contamination monitoring status, or period of hire. Positive associations were also observed for chronic myeloid leukaemia (9·57, 4·00 to 17·91, n=122) and myelodysplastic syndromes alone (3·19, 0·35 to 7·33, n=163) or combined with acute myeloid leukaemia (1·55, 0·05 to 3·42, n=598). No significant association was observed for acute lymphoblastic leukaemia (4·25, -4·19 to 19·32, n=49) or CLL (0·20, -1·81 to 2·21, n=242). A positive association was observed between radiation dose and multiple myeloma (1·62, 0·06 to 3·64, n=527) whereas minimal evidence of association was observed between radiation dose and non-Hodgkin lymphoma (0·27, -0·61 to 1·39, n=1146) or Hodgkin lymphoma (0·60, -3·64 to 4·83, n=122) mortality. This study reports a positive association between protracted low dose exposure to ionising radiation and mortality due to some haematological malignancies. Given the relatively low doses typically accrued by workers in this study (16 mGy average cumulative red bone marrow dose) the radiation attributable absolute risk of leukaemia mortality in this population is low (one excess death in 10 000 workers over a 35-year period). These results can inform radiation protection standards and will provide input for discussions on the radiation protection system. National Cancer Institute, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Institut de Radioprotection et de Sûreté Nucléaire, Orano, Electricité de France, UK Health Security Agency. For the French translation of the abstract see Supplementary Materials section.

Conversion from the frequency of chromosome translocations in T-lymphocytes to the bone marrow dose in the long-term period after internal 89,90 Sr exposure

Cytogenetic Fluorescence In Situ Hybridization studies, that allow assessing the frequency of stable chromosome aberrations in circulating T lymphocytes, are commonly used in retrospective dosimetry in cases of uniform whole-body exposure. In the event of 89,90Sr exposure, interpretation of cytogenetic data is challenging, especially if blood sampling occurs long after the start of exposure. The weighted average dose to T-lymphocytes at the time of donor blood sampling in the long-term period after exposure to 89,90Sr does not coincide with the red bone marrow dose. Previously, we developed a model that allows us to estimate the weighted average doses to T-lymphocytes upon 89,90Sr ingress into the body of people belonging to various age groups. In this study, the modeling results were used to estimate the conversion factors from the frequency of translocations to the red bone marrow dose, which is important for assessing radiobiological effects associated with hematological diseases. The objective of our study is to estimate numerically the conversion factors (Brbm) from the dose to lymphocytes to the dose to red bone marrow for various scenarios of 89,90Sr ingestion depending on age, sex, and time after the start of exposure. The following scenarios are considered: single, uniform chronic for six months, uniform chronic for 1-5 years, non-uniform intake for 5 years (simulates the dynamics of intake in the Techa riverside settlements in 1950-1954). As a result, it has been found that the Brbm values significantly depend on the age at the time of 89,90Sr intake. The older the person is at the start of exposure, the more the cytogenetic dose differs (it is significantly lower) from the dose to the red bone marrow. We can say that the cytogenetic dose corresponds to the red bone marrow dose only in newborns and infants. This is due to the age-related dynamics of T-cell populations. Sex does not have a significant effect on Brbm. The effect of the 89,90Sr intake duration on Brbm is the most pronounced for 15-year-old adolescents. For them, the difference in Brbm values for a single and chronic 5-year ingress reaches 13%. Non-uniform intake of 90Sr over several years does not have a significant effect on Brbm and can be modelled by a uniform intake of the same duration.

Investigation on Individual Variation of Organ Doses for Photon External Exposures: A Monte Carlo Simulation Study

Background: The reference dose coefficients (DCs) of the International Commission on Radiological Protection (ICRP) have been widely used to estimate organ doses of individuals for risk assessments. This approach has been well accepted because individual anatomy data are usually unavailable, although dosimetric uncertainty exists due to the anatomical difference between the reference phantoms and the individuals. We attempted to quantify the individual variation of organ doses for photon external exposures by calculating and comparing organ DCs for 30 individuals against the ICRP reference DCs.Materials and Methods: We acquired computed tomography images from 30 patients in which eight organs (brain, breasts, liver, lungs, skeleton, skin, stomach, and urinary bladder) were segmented using the ImageJ software to create voxel phantoms. The phantoms were implemented into the Monte Carlo N-Particle 6 (MCNP6) code and then irradiated by broad parallel photon beams (10 keV to 10 MeV) at four directions (antero-posterior, postero-anterior, left-lateral, right-lateral) to calculate organ DCsResults and Discussion: There was significant variation in organ doses due to the difference in anatomy among the individuals, especially in the kilovoltage region (e.g., <100 keV). For example, the red bone marrow doses at 0.01 MeV varied from 3 to 7 orders of the magnitude depending on the irradiation geometry. In contrast, in the megavoltage region (1–10 MeV), the individual variation of the organ doses was found to be negligibly small (differences <10%). It was also interesting to observe that the organ doses of the ICRP reference phantoms showed good agreement with the mean values of the organ doses among the patients in many casesConclusion: The results of this study would be informative to improve insights in individualspecific dosimetry. It should be extended to further studies in terms of many different aspects (e.g., other particles such as neutrons, other exposures such as internal exposures, and a larger number of individuals/patients) in the future.

Вычислительный фантом для дозиметрии красного костного мозга пятилетнего ребенка от инкорпорированных бета-излучателей

The red bone marrow (RBM) exposure due to bone-seeking radionuclides can lead to grave medical consequences. In particular, the increased risk of leukemia in people exposed due to contamination of the Techa River in 1950s is associated with the RBM exposure due to 89,90Sr. Improvement of the internal RBM dosimetry methods includes the development of computational phantoms that represent 3D models of the skeletal sites. Modeling radiation transport within such phantoms enables estimation of conversion factors from the radionuclide activity in the bone to the RBM dose rate. This paper is an extension study focused on generating a set of computational phantoms representing skeletons of individuals of different ages. The aim was to develop a computational phantom representing a 5-yearold child for internal RBM dosimetry from incorporated beta emitters. The phantoms of the skeletal sites with active hematopoiesis were created using the original Stochastic Parametric Skeletal Dosimetry (SPSD) method. With this method, every such site represented a set of smaller phantoms of simple geometric shape. RBM distribution across the skeleton, bone size, characteristics of bone micro-architecture, as well as density and chemical composition of the simulated media (RBM, bone) were determined based on the published data. As a result, a computational phantom of the major skeletal sites with active hematopoiesis representing a 5-year-old child was generated that included 43 phantoms of bone fragments. Linear dimensions of phantoms were within 3–75 mm. Micro-architecture parameters varied greatly: BV/TV ratio —13–52%, Tb. Th. — 0.09–0.29 mm, Tb. Sp. —0.48–0.98 mm.

Effect of Chronic Radiation Exposure on Human microRNA Expression

Relative expression of mature microRNA assessed in peripheral blood cells in persons chronically exposed to low-dose radiation in the long-term period. The study included people exposed in the 1950s on the Techa River (Southern Urals, Russia). The cumulative red bone marrow doses (RBM) of the persons in the main study group (33 persons) ranged from 77.7 to 2869.8 mGy (mean value – 698.5 mGy). The comparison group consisted of 30 people with RBM dose not exceeding 70 mGy over their lifetime. Reverse transcription of RNA samples was performed using specific stem-loop primers (“stem-loop”). Changes in the relative content of microRNA were assessed by real-time PCR on the CFX96 detection system (BioRad, USA). Statistical analysis of the results was performed using Mann–Whitney U-criterion. A significant increase in hsa-miR-125b, hsa-miR-181a, and hsa-miR-16-5p content was detected in exposed people after 60 years, and their expression was found to depend on the RBM dose.

Medical imaging utilization and associated radiation exposure in children with down syndrome.

To evaluate the frequency of medical imaging or estimated associated radiation exposure in children with Down syndrome. This retrospective cohort study included 4,348,226 children enrolled in six U.S. integrated healthcare systems from 1996-2016, 3,095 of whom were diagnosed with Down syndrome. We calculated imaging rates per 100 person years and associated red bone marrow dose (mGy). Relative rates (RR) of imaging in children with versus without Down syndrome were estimated using overdispersed Poisson regression. Compared to other children, children with Down syndrome received imaging using ionizing radiation at 9.5 times (95% confidence interval[CI] = 8.2-10.9) the rate when age <1 year and 2.3 times (95% CI = 2.0-2.5) between ages 1-18 years. Imaging rates by modality in children <1 year with Down syndrome compared with other children were: computed tomography (6.6 vs. 2.0, RR = 3.1[95%CI = 1.8-5.1]), fluoroscopy (37.1 vs. 3.1, RR 11.9[95%CI 9.5-14.8]), angiography (7.6 vs. 0.2, RR = 35.8[95%CI = 20.6-62.2]), nuclear medicine (6.0 vs. 0.6, RR = 8.2[95% CI = 5.3-12.7]), radiography (419.7 vs. 36.9, RR = 11.3[95%CI = 10.0-12.9], magnetic resonance imaging(7.3 vs. 1.5, RR = 4.2[95% CI = 3.1-5.8]), and ultrasound (231.2 vs. 16.4, RR = 12.6[95% CI = 9.9-15.9]). Mean cumulative red bone marrow dose from imaging over a mean of 4.2 years was 2-fold higher in children with Down syndrome compared with other children (4.7 vs. 1.9mGy). Children with Down syndrome experienced more medical imaging and higher radiation exposure than other children, especially at young ages when they are more vulnerable to radiation. Clinicians should consider incorporating strategic management decisions when imaging this high-risk population.

#5819 HAEMODIALYSIS EFFECT ON METABOLIC THERAPY WITH [131INA]: A COMPARATIVE STUDY

Abstract Background and Aims The use of [131INa] therapy in patients undergoing haemodialysis (HD) is still controversial. Considering that the main elimination of 131I is urinary and the sessions of HD take place in wards full of other patients, various modifications should be made in the therapy. Due to the limited bibliography and the lack of consensus in clinical guidelines we developed this comparative study between two patients on HD treated with [131INa]. External dose rate measurement (EDRM), time of hospitalization, timing of dialysis after the administration of [131INa] and the status of contamination of dialysis machine were considered. Method Two patients on HD were treated with [131INa] in June 2021. A 74years old women with hyperthyroidism due to a multinodular goitre, resistant to antithyroid drugs (PT1). A 49years old man candidate to ablation treatment with low activity of [131INa] after a total thyroidectomy due to differentiated thyroid cancer (pT2N0) (PT2). The recommended activity was administered according to clinical indication. PT1 received 555MBq and PT2 received 1110 MBq of [131INa] in Metabolic Therapy Unit (MTU) after the first HD session in the nephrology ward. The following HD sessions were in MTU (Wed.-Fri.). High-flux dialysis was performed using a Reverse Osmosis portable system. The hospital stay was 5 days (Mo at Fri) for each patient. EDRM at 1 meter was measured three times a day. Liquid samples from HD machine (dialysis fluid, water wash) were obtained every day at the same time before and after each session and radioactivity was analysed. Results EDRM after second HD at discharge was 12 and 7,4mcSv/h in PT1 and PT2 respectively. After first HD both patients reached EDR &amp;lt;40mcSv/h (22 and18 mcSv/h). Red bone marrow dose was 130,76mGy and 110,42mGy respectively. Radioactivity in dialysis fluid was: 0,00999MBq PT1- 0,00259MBq PT2 after first HD; 0,0022MBq PT1- 0,00074MBq PT2 after second HD. No radioactivity was detected in wash water of dialysis equipment in both patients during each HD session. There was no secondary complications due to overhydration or dyslectrolythemias. Conclusion External dose rate measurement is key to decide if patients undergoing HD are ready to be discharge. Once EDRM &amp;lt;40mcSv/h at 1 meter has been reached, patients could immediately return to their dialysis centre following the protection radiology rules and so we must always respect the distance between the patients, if that cannot be performed the session will be in the hospital. There is no need to modify radioiodine activities neither timing of HD sessions as red bone marrow dose do not exceed recommended value (2Gy). There is no contamination of HD machine, it could be used after usual decontamination for other patients.

Оценка влияния хронического облучения на преждевременное старение Т-лимфоцитов человека на основе нестабильных хромосомных аберраций

For more than 60 years, residents of the villages on the Techa River have been chronically exposed to combined radiation, receiving a wide range of doses. Red bone marrow (RBM) is the critical system in the exposure conditions. This study aimed to assess the effect of chronic exposure on premature aging of T-lymphocytes based on the frequency of unstable chromosome aberrations; the subjects were the residents of the Southern Urals that have been chronically exposed to radiation. The increased frequency of occurrence of dicentrics and rings in T-cells of the exposed persons was the marker of cellular aging, with the associated doses to the red bone marrow (RBM dose) at 0.5–2.5 Gy. The participants (RBM donors), both exposed and non-exposed, were divided into three age subgroups: 40–59 years old, 60–69 years old, 70–79 years old. The differences in the RBM dose among the exposed individuals were insignificant. In the exposed group, unstable chromosome aberrations (UCA) were recorded significantly more often than in the control group (p = 0.04). The age group of 40–59 years was the one where the exposed donors had significantly more frequently occurring chromosome aberrations compared to the non-exposed participants. There were no such differences registered in other age groups. The age-associated increase of the amount of chromosome aberrations was registered in the non-exposed group only. Chronic exposure to radiation indirectly promotes premature aging of T-lymphocytes: 1) in the long term, the exposed individuals had UCA significantly more often; 2) compared to the control group, the 40–59 years age subgroup of the exposed group had increased cytogenetic index. In the context of this study, the number of dicentrics and rings was not registered as increasing in the older age subgroups of exposed individuals, which may be due to the specifics of the donor inclusion criteria, which, for the elderly, may favor radioresistant individuals.

ВЛИЯНИЕ ХРОНИЧЕСКОГО ОБЛУЧЕНИЯ И ФАКТОРОВ НЕРАДИАЦИОННОЙ ПРИРОДЫ НА ВНУТРИКЛЕТОЧНУЮ КОНЦЕНТРАЦИЮ STAT3

Purpose: To evaluate the influence of radiation and non-radiation factors on the intracellular concentration of the transcription factor STAT3 in peripheral blood lymphocytes of chronically irradiated residents of the coastal villages of the Techa River in the long-term after the onset of irradiation. Material and methods: The main group consisted of 50 people aged 67 to 84 years old with an average dose of irradiation of the red bone marrow of 727.9±79.1 mGy; thymus and peripheral lymphoid organs – 85.9±13.6 mGy. The comparison group included 25 people aged from 61 to 87 who were not exposed to accidents, whose distribution by sex and ethnicity corresponded to the composition of the main group. Peripheral blood lymphocyte lysates were normalized for total protein concentration prior to enzyme immunoassay. Results: The median intracellular concentration of STAT3 was 167.6 (118.3–240.1) pg/ml in the main group and 147.0 (116.7–179.2) pg/ml in the control group. Conclusion: The intracellular level of STAT3 did not differ significantly between chronically exposed and non-exposed individuals, as well as in people from different dose subgroups. Correlations between the concentration of STAT3 and dose characteristics, gender and ethnicity of the examined people were not found. In people with a red bone marrow dose of 0.85 Gy or more, STAT3 concentration correlated with age at the time of examination (SR= ‒0.67, p=0.01). In other dose subgroups, no correlation was found between the estimated indicator and the achieved age. The results are preliminary.

Doses from external irradiation and ingestion of 134Cs, 137Cs and 90Sr of the population of Belarus accumulated over 35years after the Chernobyl accident.

This study considers the exposure of the population of the most contaminated Gomel and Mogilev Oblasts in Belarus to prolonged sources of irradiation resulting from the Chernobyl accident. Dose reconstruction methods were developed and applied in this study to estimate the red bone-marrow doses (RBMs) from (i) external irradiation from gamma-emitting radionuclides deposited on the ground and (ii) 134Cs, 137Cs and 90Sr ingestion with locally produced foodstuffs. The mean population-weighted RBM doses accumulated during 35years after the Chernobyl accident were 12 and 5.7mGy for adult residents in Gomel and Mogilev Oblasts, respectively, while doses for youngest age groups were 20-40% lower. The highest mean area-specific RBM doses for adults accumulated in 1986-2021 were 63, 56 and 46mGy in Narovlya, Vetka and Korma raions in Gomel Oblast, respectively. For most areas, external irradiation was the predominant pathway of exposure (60-70% from the total dose), except for areas with an extremely high aggregated 137Cs soil to cow's milk transfer coefficient (≥ 5.0Bq L-1 per kBq m-2), where the contribution of 134Cs and 137Cs ingestion to the total RBM dose was more than 70%. The contribution of 90Sr intake to the total RBM dose did not exceed 4% for adults and 10% for newborns in most raion in Gomel and Mogilev Oblasts. The validity of the doses estimated in this study was assessed by comparison with doses obtained from measurements by thermoluminescence dosimeters and whole-body counters done in 1987-2015. The methodology developed in this study can be used to calculate doses to target organs other than RBM such as thyroid and breast doses. The age-dependent and population-weighted doses estimated in this study are useful for ecological epidemiological studies, for projection of radiation risk, and for justification of analytical epidemiological studies in populations exposed to Chernobyl fallout.

Low-dose ionizing radiation exposure and risk of leukemia: results from 1950–1995 Chinese medical X-ray workers’ cohort study and meta-analysis

BackgroundIt has been well-established that acute radiation exposures increase the risk of leukemia. However, it is still unknown whether these leukemia risk estimates could be extrapolated to occupational populations who receive repeated low-dose radiation exposure. The purpose of this study was to estimate quantified associations between low-dose radiation exposures and leukemia. MethodsThe Chinese medical X-ray worker study (CMXW) included 27,011 medical X-ray workers employed at major hospitals in 24 provinces in China from 1950 to 1980, and a control population of 25,782 physicians matched by hospital, who were unexposed to X-ray equipment. Poisson regression models were used to estimate the excess relative risk (ERR) and excess absolute risk (EAR) for the incidence of leukemia associated with cumulative doses. A meta-analysis of the published literature on low-dose occupational radiation exposure and leukemia risk was also conducted. ResultsThe incidence rates of leukemia in X-ray workers and the control group were 6.70 and 3.39 per 100,000 person-years, respectively. Among X-ray workers, the average cumulative red bone marrow dose was 0.046 Gy. We found a positive relationship between 2-year lagged cumulative red bone marrow dose and risk of leukemia excluding chronic lymphocytic leukemia (CLL) (ERR = 0.66 per 100 mGy, 90% CI: 0.09, 1.53; EAR = 0.29 per 104 PY-100 mGy, 90% CI: 0.07, 0.56). The excess risk was largely driven by myeloid leukemia (ERR = 1.06 per 100 mGy, 90% CI: 0.22, 2.51). Based on the meta-analysis, the pooled ERR at 100 mGy was 0.19 (95% CI: 0.08, 0.31). ConclusionThis study provides strong evidence of a positive and linear doseresponse relationship between cumulative red bone marrow dose and the incidence of non-CLL leukemia.

Epidemiological studies of CT scans and cancer risk: the state of the science.

20 years ago, 3 manuscripts describing doses and potential cancer risks from CT scans in children raised awareness of a growing public health problem. We reviewed the epidemiological studies that were initiated in response to these concerns that assessed cancer risks from CT scans using medical record linkage. We evaluated the study methodology and findings and provide recommendations for optimal study design for new efforts. We identified 17 eligible studies; 13 with published risk estimates, and 4 in progress. There was wide variability in the study methodology, however, which made comparison of findings challenging. Key differences included whether the study focused on childhood or adulthood exposure, radiosensitive outcomes (e.g. leukemia, brain tumors) or all cancers, the exposure metrics (e.g. organ doses, effective dose or number of CTs) and control for biases (e.g. latency and exclusion periods and confounding by indication). We were able to compare results for the subset of studies that evaluated leukemia or brain tumors. There were eight studies of leukemia risk in relation to red bone marrow (RBM) dose, effective dose or number of CTs; seven reported a positive dose-response, which was statistically significant (p < 0.05) in four studies. Six of the seven studies of brain tumors also found a positive dose-response and in five, this was statistically significant. Mean RBM dose ranged from 6 to 12 mGy and mean brain dose from 18 to 43 mGy. In a meta-analysis of the studies of childhood exposure the summary ERR/100 mGy was 1.78 (95%CI: 0.01-3.53) for leukemia/myelodisplastic syndrome (n = 5 studies) and 0.80 (95%CI: 0.48-1.12) for brain tumors (n = 4 studies) (p-heterogeneity >0.4). Confounding by cancer pre-disposing conditions was unlikely in these five studies of leukemia. The summary risk estimate for brain tumors could be over estimated, however, due to reverse causation. In conclusion, there is growing evidence from epidemiological data that CT scans can cause cancer. The absolute risks to individual patients are, however, likely to be small. Ongoing large multicenter cohorts and future pooling efforts will provide more precise risk quantification.

Residential exposure to natural background radiation at birth and risk of childhood acute leukemia in France, 1990–2009

BackgroundThe role of natural background radiation (NBR) in childhood acute leukemia (AL) remains unclear. Several large record based studies have recently reported heterogeneous results. Differences in exposure assessment timing may explain this heterogeneity. ObjectivesIn a previous ecological study we did not observe any association between childhood AL incidence in France and NBR exposure at the time of diagnosis. With the same methodology, the present study focused on NBR exposure at the time of birth. Based on data from the French national registry of childhood cancer, we analyzed all AL together, and lymphoblastic and myeloid AL, separately. MethodsWe included 6,059 childhood AL cases born and diagnosed in mainland France between 1990 and 2009. NBR levels in municipalities of residence at birth were estimated by cokriging models, using NBR measurements and precise geological data. The incidence rate ratio (IRR) per unit variation of exposure was estimated with Poisson regression models, with adjustment for socio-demographic indicators and ultraviolet radiation levels. NBR exposures were considered at the time of birth, and cumulatively from birth to diagnosis. We also estimated a total NBR dose to red-bone marrow (RBM). ResultsThere was no evidence for an association between NBR exposure at birth and childhood AL incidence, neither overall (gamma radiation: IRR = 0.99 (0.94,1.05) per 50 nSv/h; radon: IRR = 0.97 (0.91,1.03) per 100 Bq/m3) nor for the main AL types. The conclusions were similar with the cumulative exposures, and the total RBM dose. ConclusionsThe study was based on high quality incidence data, large numbers of AL cases, and validated models of NBR exposure assessment. In all, the results further support the hypothesis that NBR are not associated to childhood AL in France.

Tables for effective dose assessment from diagnostic radiology (period 1946–1995) in epidemiologic studies

Diagnostic radiology is a leading cause of man-made radiation exposure to the population. It is an important factor in many epidemiological studies as variable of interest or as potential confounder. The effective dose as a risk related quantity is the most often stated patient dose. Nevertheless, there exists no comprehensive quantification model for retrospective analysis for this quantity. This paper gives a catalog of effective dose values for common and rare examinations and demonstrates how to modify the dose values to adapt them to different calendar years using a quantification concept already used for retrospective analysis of the red bone marrow dose. It covers the time period of 1946 to 1995 and allows considering technical development and different practical standards over time. For an individual dose assessment, if the dose area product is known, factors are given for most examinations to convert the dose area product into the effective dose. Additionally factors are stated for converting the effective dose into the red bone marrow dose or vice versa.

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

Concept of T-Cell Genus as a Basis for Analysis of the Results of Cytogenetic Studies after Local Bone Marrow Exposure

Evaluation of the frequency of chromosome translocations in peripheral blood T-lymphocytes is a generally accepted method of retrospective biodosimetry. Accidental contamination of the Techa River (Chelyabinsk Oblast) in 1950s with bone-seeking long-lived strontium-90 gave an opportunity to evaluate the effect of local red bone marrow (RBM) exposure on translocation formation in the peripheral T-lymphocytes of local inhabitants. The studies of the inhabitants using fluorescent in situ hybridization (FISH) showed that RBM doses calculated based on FISH results were lower than those estimated based on 90Sr body burden measurements. The current study presents analytical review of the published data dealing with the most important processes of the T-lymphocyte development and formation of chromosome aberrations: characteristics of the main compartments where the exposure of T-cell occurs; assessment of the time spent by T-lymphocytes and their progenitors in these compartments; analysis of the dynamics of T-cell populations (proliferation and death); age-related aspects. The paper presents a concept of T-cell Genus (TG) united all the progeny of T progenitor with inheritable specific aberrations that could have developed in bone marrow.

Радиационный риск заболеваемости и смертности от лейкоза в объединенной когорте работников атомной отрасли России и Великобритании

Purpose: The estimation of the radiation risk of leukemia incidence and mortality for occupational exposure.&#x0D; Material and methods: The study was conducted in the pooled cohort comprised 45,817 workers from the two enterprises; 23,443 radiation workers first employed in 1947–2002 from the Sellafield plant (Great Britain) and 22,774 workers from the Mayak PA (Russia) first employed at the main plants in 1948–1982. The period of follow-up was terminated at the end of 2008 for Mayak workers who were Ozyorsk city residents, and at the end of 2005 for Sellafield workers and Mayak workers who had migrated from Ozyorsk.&#x0D; Results: Comparable radiation risk estimates of leukemia incidence and mortality were found among Mayak PA and Sellafield workers as for the whole dose range and separate dose intervals. Averaged by attained age estimate of excess relative risk per 1 Gy of external gamma-dose was 3.0 (95 % CI: 1.3–6.3) under the assumption of the linear dose–effect model. The quadratic model with attained age modification showed the best quality of fit. Risk estimates were statistically significant in the dose range 0.15–1.5 Gy. There was no evidence of any relationship between leukemia risks and accumulated red bone marrow dose of internal alpha-exposure due to incorporated Pu-239.&#x0D; Conclusion: Preliminary analysis of the pooled cohort data has demonstrated the feasibility and efficiency of a research project looking at leukemia risks in a joint cohort of Mayak and Sellafield workers. The current study provides further evidence about the already well established link between external-gamma exposure and leukemia risk. However, it fails to provide any firm further evidence about the absence or presence of relationship between plutonium exposure and leukemia risk.

Mortality among U.S. military participants at eight aboveground nuclear weapons test series

Background Approximately 235,000 military personnel participated at one of 230 U.S. atmospheric nuclear weapons tests from 1945 through 1962. At the Nevada Test Site (NTS), the atomic veterans participated in military maneuvers, observed nuclear weapons tests, or provided technical support. At the Pacific Proving Ground (PPG), they served aboard ships or were stationed on islands during or after nuclear weapons tests. Material and methods Participants at seven test series, previously studied with high-quality dosimetry and personnel records, and the first test at TRINITY formed the cohort of 114,270 male military participants traced for vital status from 1945 through 2010. Dose reconstructions were based on Nuclear Test Personnel Review records, Department of Defense. Standardized mortality ratios (SMR) and Cox and Poisson regression models were used in the analysis. Results Most atomic veterans were enlisted men, served in the Navy at the PPG, and were born before 1930. Vital status was determined for 96.8% of the veterans; 60% had died. Enlisted men had significantly high all-causes mortality SMR (1.06); officers had significantly low all-causes mortality SMR (0.71). The pattern of risk over time showed a diminution of the ‘healthy soldier effect’: the all-causes mortality SMR after 50 years of follow-up was 1.00. The healthy soldier effect for all cancers also diminished over time. The all-cancer SMR was significantly high after 50 years (SMR 1.10) primarily from smoking-related cancers, attributed in part to the availability of cigarettes in military rations. The highest SMR was for mesothelioma (SMR 1.56) which was correlated with asbestos exposure in naval ships. Prostate cancer was significantly high (SMR 1.13). Ischemic heart disease was significantly low (SMR 0.84). Estimated mean doses varied by organ were low; e.g., the mean red bone marrow dose was 6 mGy (maximum 108 mGy). Internal cohort dose–response analyses provided no evidence for increasing trends with radiation dose for leukemia (excluding chronic lymphocytic leukemia (CLL)) [ERR (95% CI) per 100 mGy −0.37 (−1.08, 0.33); n = 710], CLL, myelodysplastic syndrome, multiple myeloma, ischemic heart disease, or cancers of the lung, prostate, breast, and brain. Conclusion No statistically significant radiation associations were observed among 114,270 nuclear weapons test participants followed for up to 65 years. The 95% confidence limits were narrow and excluded mortality risks per unit dose that are two to four times higher than those reported in other investigations. Significantly elevated SMRs were seen for mesothelioma and asbestosis, attributed to asbestos exposure aboard ships.

Radiation exposure from computerized tomography and risk of childhood leukemia: Finnish register-based case-control study of childhood leukemia (FRECCLE).

The only well-established risk factors for childhood leukemia are high-dose ionizing radiation and Down syndrome. Computerized tomography is a common source of low-dose radiation. In this study, we examined the magnitude of the risk of childhood leukemia after pediatric computed tomography examinations. We evaluated the association of computed tomography scans with risk of childhood leukemia in a nationwide register-based case-control study. Cases (n=1,093) were identified from the population-based Finnish Cancer Registry and three controls, matched by gender and age, were randomly selected for each case from the Population Registry. Information was also obtained on birth weight, maternal smoking, parental socioeconomic status and background gamma radiation. Data on computed tomography scans were collected from the ten largest hospitals in Finland, covering approximately 87% of all pediatric computed tomography scans. Red bone marrow doses were estimated with NCICT dose calculation software. The data were analyzed using exact conditional logistic regression analysis. A total of 15 cases (1.4%) and ten controls (0.3%) had undergone one or more computed tomography scans, excluding a 2-year latency period. For one or more computed tomography scans, we observed an odds ratio of 2.82 (95% confidence interval: 1.05 – 7.56). Cumulative red bone marrow dose from computed tomography scans showed an excess odds ratio of 0.13 (95% confidence interval: 0.02 – 0.26) per mGy. Our results are consistent with the notion that even low doses of ionizing radiation observably increase the risk of childhood leukemia. However, the observed risk estimates are somewhat higher than those in earlier studies, probably due to random error, although unknown predisposing factors cannot be ruled out.

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

The fluorescence in situ hybridization (FISH) technique allows for the estimation of the number of stable chromosomal aberrations (translocations) in human blood T-lymphocytes decades after radiation exposure. Therefore, it is used for retrospective assessment of irradiation doses received by red bone marrow (RBM). Cytogenetic analysis of individuals exposed on the Techa River in the 1950s to 89,90Sr, locally irradiating RBM, showed that dose assessment based on FISH data led to underestimation of the actual dose estimated from measurements of whole-body 90Sr content. The purpose of current study was to evaluate the dose–effect relationship and the frequency of translocations per 1 Gy of RBM irradiation dose and T-lymphocytes dose for donors living in Techa riverside villages (n = 178; translocation yield = 2389; number of genome equivalents GE = 96 446). Irradiation doses were estimated using the latest version of the Techa River dosimetry system and the T-cell irradiation model. Statistical analysis showed that the frequency of translocations per 1000 GE per 1 Gy of RBM dose was 8.0 ± 0.7; this value was statistically significantly lower than the value estimated for Sellafield radiation workers under external exposure (11.6 ± 1.6). At the same time, the use of T-cell and their progenitor doses led to re-evaluation (increase) in the slope of the dose–response curve to 11.8 ± 1.6 per 1 Gy per 1000 GE, which agreed well with the published data. The obtained estimates of the background frequencies of translocations also were close to the published values ​​for unexposed donors. These findings demonstrate the legitimacy of using a model approach for estimation of irradiation doses in T-lymphocytes and their progenitors and the need to take into account complex T-cell dynamics in interpretation of cytogenetic data for the purposes of biodosimetry.