Quantitative evaluation of radon, tobacco use and lung cancer association in an occupational cohort with 27 follow-up years.

BACKGROUND: Occupational radon cohorts provide important information about exposure at residential level, which are difficult to observe prospectively. However, evidence about radon-related lung cancer risks from initial exposure in childhood or interaction between radon and smoking is still limited. METHODS: A total of 6017 tin miners with at least 10 years of underground radon exposure were enrolled beginning in 1992 and followed for up to 27 years. Lung cancer risks were estimated by modeling total and intensity of radon exposure. RESULTS: A total of 933 lung cancer cases occurred in this cohort over 89,092 person-years of follow up. Excess relative risk increased by 0.96% per cumulative working level month (WLM). A unique aspect of this population was the early age at first radon exposure for workers. Results showed that lung cancer risk from initial radon exposure in childhood (<13 years old) was greater than risk when first exposure occurred at later ages (13-17, 18-24, and ≥ 25 years old). Moreover, risk declined with years since last exposure and attained age, but increased with age at last exposure. Importantly, these patterns were stable after adjustment for tobacco use or arsenic exposure. For joint effects of radon and other agents, our results support sub-multiplicative as the most likely model for interaction between radon and tobacco use or arsenic exposure. CONCLUSION: This study highlights the possible importance of radon exposure in childhood in cancer etiology and suggests another potential strategy to mitigate the global lung cancer burden.

Radon and cancer mortality among underground uranium miners in the Príbram region of the Czech Republic.

BACKGROUND: This study aims to estimate the association between radon and site-specific cancer mortality among a large contemporary cohort of male uranium miners. METHODS: Annual occupational radon exposure was estimated based on a worker's duration of underground mining in a year and estimates of potential alpha energy of radon progeny in their location of work. Cancer mortality over the period 1977-1992 was ascertained for a cohort of 16 434 male underground uranium miners employed in the Czech Republic between 1946 and 1992. Poisson regression was used to estimate relationships between cumulative radiation exposure (in working level months [WLM]) and site-specific cancer mortality. RESULTS: Radon is positively associated with lung cancer mortality (excess relative rate [ERR] per 100 WLM = 0.2; 95% confidence interval [CI]: 0.10, 0.37). The best fit of the dose-response relationship between radon and lung cancer mortality was linear and estimates of radon-lung cancer associations varied by windows of time-since-exposure. Positive associations between radon and several types of cancer other than lung cancer were identified, notably chronic lymphocytic leukemia (CLL) (ERR/100 WLM = 0.24; 95% CI: [not determined [ND], 5.10]) and extrathoracic cancer (ERR/100 WLM = 0.12; 95% CI: [ND, 0.69]). We observed no associations between radon and stomach cancer, nor between radon and several hematopoietic cancer subtypes. CONCLUSIONS: This study confirms the established radon-lung cancer association and suggests that radon may also be associated with other types of cancer mortality. Further investigations of extrathoracic and CLL cancer, with the aim of obtaining more precise estimates, are warranted to understand associations between radon and cancers other than lung.

Age-dependent ingestion and inhalation doses due to intake of uranium and radon in water samples of Shiwalik Himalayas of Jammu and Kashmir, India.

The research work involved the ingestion and inhalation doses due to the intake of radon and uranium through water samples used by the inhabitants, measured in the villages of the Shiwalik Himalayas of Jammu and Kashmir, India. The uranium concentration in collected water samples was assessed by LED fluorimetric technique. All values of doses were found to be below the proposed limit of 100 µSv year-1 for all age categories except for infants due to the high-dose conversion factor. The annual effective doses for the various body organs due to the intake of radon was also calculated and found the maximum dose for lungs than other organs. The concentration of radon in water samples was assessed by Smart Rn Duo portable monitor and compared with RAD7. Statistical analysis was carried out and the Shapiro and Wilk (Biometrika, 52(3/4), 591-611, 1965) test has been also used for the distribution of the data. The physicochemical parameters were also measured in the collected water samples.

QUANTITATIVE ANALYSIS OF THE POTENTIAL ROLE OF BASAL CELL HYPERPLASIA IN THE RELATIONSHIP BETWEEN CLONAL EXPANSION AND RADON CONCENTRATION.

Applying the two-stage clonal expansion model to epidemiology of lung cancer among uranium miners, it has been revealed that radon acts as a promoting agent facilitating the clonal expansion of already mutated cells. Clonal expansion rate increases non-linearly by radon concentration showing a plateau above a given exposure rate. The underlying mechanisms remain unclear. Earlier we proposed that progenitor cell hyperplasia may be induced upon chronic radon exposure. The objective of the present study is to test whether the induction of hyperplasia may provide a quantitative explanation for the plateau in clonal expansion rate. For this purpose, computational epithelium models were prepared with different number of basal cells. Cell nucleus hits were computed by an own-developed Monte-Carlo code. Surviving fractions were estimated based on the number of cell nucleus hits. Cell division rate was computed supposing equilibrium between cell death and cell division. It was also supposed that clonal expansion rate is proportional to cell division rate, and therefore the relative increase in cell division rate and clonal expansion rate are the same functions of exposure rate. While the simulation results highly depend on model parameters with high uncertainty, a parameter set has been found resulting in a cell division rate-exposure rate relationship corresponding to the plateau in clonal expansion rate. Due to the high uncertainty of the applied parameters, however, further studies are required to decide whether the induction of hyperplasia is responsible for the non-linear increase in clonal expansion rate or not. Nevertheless, the present study exemplifies how computational modelling can contribute to the integration of observational and experimental radiation protection research.

Genetic modifiers of radon-induced lung cancer risk: a genome-wide interaction study in former uranium miners.

PURPOSE: Radon is a risk factor for lung cancer and uranium miners are more exposed than the general population. A genome-wide interaction analysis was carried out to identify genomic loci, genes or gene sets that modify the susceptibility to lung cancer given occupational exposure to the radioactive gas radon. METHODS: Samples from 28 studies provided by the International Lung Cancer Consortium were pooled with samples of former uranium miners collected by the German Federal Office of Radiation Protection. In total, 15,077 cases and 13,522 controls, all of European ancestries, comprising 463 uranium miners were compared. The DNA of all participants was genotyped with the OncoArray. We fitted single-marker and in multi-marker models and performed an exploratory gene-set analysis to detect cumulative enrichment of significance in sets of genes. RESULTS: We discovered a genome-wide significant interaction of the marker rs12440014 within the gene CHRNB4 (OR = 0.26, 95% CI 0.11-0.60, p = 0.0386 corrected for multiple testing). At least suggestive significant interaction of linkage disequilibrium blocks was observed at the chromosomal regions 18q21.23 (p = 1.2 × 10-6), 5q23.2 (p = 2.5 × 10-6), 1q21.3 (p = 3.2 × 10-6), 10p13 (p = 1.3 × 10-5) and 12p12.1 (p = 7.1 × 10-5). Genes belonging to the Gene Ontology term "DNA dealkylation involved in DNA repair" (GO:0006307; p = 0.0139) or the gene family HGNC:476 "microRNAs" (p = 0.0159) were enriched with LD-blockwise significance. CONCLUSION: The well-established association of the genomic region 15q25 to lung cancer might be influenced by exposure to radon among uranium miners. Furthermore, lung cancer susceptibility is related to the functional capability of DNA damage signaling via ubiquitination processes and repair of radiation-induced double-strand breaks by the single-strand annealing mechanism.

Indoor Radon Gas (222Rn) Levels in Homes in Aldama, Chihuahua, Mexico and the Risk of Lung Cancer.

Radon (222Rn) is an odorless and tasteless gas that is known to cause lung cancer. The objective of this research was to quantify the levels of exposure to radon among people living in an environment rich in uranium (U). Radon concentrations were measured for 3 days in 12 homes in Aldama, Mexico. Homeowners agreed to participate in the study; hence, the sample was non-probabilistic. Radon was measured with a portable AlphaGuard Radon Monitor (Genicron Instruments GmbH), which was placed in a bedroom of each home at a height of 0.74 m. Gas levels were registered in Becquerels (Bq m−3), with readings taken every 10 min along with readings of ambient temperature (AT), air pressure (AP), and relative humidity (RH). We found that radon gas levels in Aldama exceed the maximum permissible limits (USA: 148 Bq m−3). Levels were higher at night, and were above the maximum permissible level recommended by the International Atomic Energy Agency of the United Nations (<200 Bq m−3). Most residents in the area have family histories of lung problems, but it was difficult to establish a strong correlation between 222Rn and lung cancer. Federal, state, and municipal governments should take stronger action to reduce the effects of radon gas on communities.

COMPARATIVE STUDY OF RADON EXPOSURE IN CANADIAN HOMES AND URANIUM MINES-A DISCUSSION ON THE IMPORTANCE OF NATIONAL RADON PROGRAM.

The history of lung cancer in uranium miners is well known for over hundreds of years when the disease was referred to as 'miner's disease' or 'mountain sickness'. Radon levels in uranium mines have decreased significantly over the past 30 years as a result of effective radiation protection measures at workplaces. For the most recent 10-year period, the average radon concentrations to underground and surface workers in Canadian uranium mines were 111 and 11 Bq m-3, respectively. Based on the recent radon survey carried out in roughly 14 000 homes in 121 health regions across Canada and the more recent radon and thoron survey in 33 Canadian cities and 4000 homes, the average radon concentration in Canadian homes is 77 Bq m-3. This study demonstrates that, nowadays, workers are exposed to radon in underground mines at a comparable radon level to what Canadians are exposed to at home. Since exposure to indoor radon is the main source of natural radiation exposure to the population, it is important for the National Radon Program to further increase radon awareness, and to encourage more Canadians to take appropriate actions to reduce radon exposure.

Validation of Comet assay in Oregon-R and Wild type strains of Drosophila melanogaster exposed to a natural radioactive environment in Brazilian semiarid region.

Natural radiation of geological origin is a common phenomenon in Brazil, a country where radioactive agents such as uranium may be often found. As an unstable atom, uranium undergoes radioactive decay with the generation of a series of decay by-products, including radon, which may be highly genotoxic and trigger several pathological processes, among which cancer. Because it is a gas, radon may move freely between cracks and gaps in the ground, seeping upwards into the buildings and in the environment. In this study, two Drosophila melanogaster Meigen (Diptera, Drosophilidae) strains called Oregon-R and Wild (collected in a non-radioactive environment) were exposed to atmospheric radiation in the Lajes Pintadas city, in the semiarid zone of northeastern Brazil. After six days of environmental exposure, the organisms presented genetic damage significantly higher than that of the negative control group. The genotoxic effects observed reinforce the findings of other studies carried out in the same region, which warn about the environmental risks related to natural radioactivity occurrence. The results also validate the use of the Comet assay in hemocytes of D. melanogaster as a sensitive test to detect genotoxicity caused by natural radiation, and the use of a recently collected D. melanogaster strain in the environmental of radon.

[Assessment of radon-induced health risk for occupants of a house built on uranium ore residue]. / Évaluation des risques sanitaires induits par le radon pour les occupants d'une maison construite sur des résidus de minerais d'uranium.

BACKGROUND: At the request of French public authorities, the Institute of Radiological Protection and Nuclear Safety has assessed the radiological situation of a house built on uranium ore residues in Haute-Vienne and the health risks induced from exposure to radon for all occupants. Classified as a lung carcinogen by the World Health Organization, radon is a proven cause of lung cancer in case of regular inhalation over a long period, and the risk increases with cumulative exposure. METHODS: Radon exposure was reconstructed for various standard profiles of house occupancy. A risk model derived from a European epidemiological study was used to calculate the lifetime probability of death from lung cancer according to these standard profiles. RESULTS: Risk assessment of the occupants of the house highlighted the following main findings. For a resident school child having been exposed to radon from birth to the age of 7, the lifetime relative risk (LRR) was estimated at 5. For last adult and young adult residents having lived more than 10years in the house, the probability of death from lung cancer was in the same order of magnitude as that of a regular cigarette smoker, with a LRR from 10 to 13 and a lifetime probability of death from lung cancer between 3 and 4%. If these individuals smoked regularly, in addition to being exposed to radon, this probability would be between 6 and 32% (supposing an additive or multiplicative interaction). CONCLUSION: For former occupants (non-smokers) having been exposed 10years during childhood, the LRR was two-fold lower. For children having been in day care in the house, the increased probability of death from lung cancer was low, with a LRR lower than 2. Supposing, as in adults, that the risk decreases beyond 30years after the end of radon exposure, the increase was almost zero for former occupants exposed during childhood and during day care, with a LRR close to 1.

Mechanistic study on lung cancer mortality after radon exposure in the Wismut cohort supports important role of clonal expansion in lung carcinogenesis.

Lung cancer mortality after radon exposure in the Wismut cohort was analyzed using the two-stage clonal expansion (TSCE) model. A total of 2996 lung cancer deaths among the 58,695 male workers were observed during the follow-up period between 1946 and 2003. Adjustment to silica exposure was performed to find a more accurate estimation of the risk of radon exposure. An additional analysis with the descriptive excess relative risk (ERR) model was carried out for comparison. The TSCE model that best describes the data is nonlinear in the clonal expansion with radon exposure and has a saturation level at an exposure rate of [Formula: see text]. The excess relative risk decreases with age and shows an inverse exposure rate effect. In comparison with the ERR model, the TSCE model predicts a considerably larger risk for low exposures rates below [Formula: see text]. Comparison to other mechanistic studies of lung cancer after exposure to alpha particles using the TSCE model reveals an extraordinary consistency in the main features of the exposure response, given the diversity in the characteristics of the cohorts and the exposure across different studies. This suggests that a nonlinear response mechanism in the clonal expansion, with some level of saturation at large exposure rates, may be playing a crucial role in the development of lung cancer after alpha particle irradiation.

Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners.

BACKGROUND: High radon exposure is a risk factor for squamous cell carcinoma, a major lung cancer histology observed in former uranium miners. Radon exposure can cause oxidative stress, leading to pulmonary inflammation. Interleukin-6 (IL-6) is a pro-carcinogenic inflammatory cytokine that plays a pivotal role in lung cancer development. OBJECTIVES: We assessed whether single nucleotide polymorphisms (SNPs) in the IL6 promoter are associated with lung cancer in former uranium miners with high occupational exposure to radon gas. METHODS: Genetic associations were assessed in a case-control study of former uranium miners (242 cases and 336 controls). A replication study was performed using data from the Gene Environment Association Studies (GENEVA) Genome Wide Association Study (GWAS) of Lung Cancer and Smoking. Functional relevance of the SNPs was characterized using in vitro approaches. RESULTS: We found that rs1800797 was associated with squamous cell carcinoma in miners and with a shorter time between the midpoint of the period of substantial exposure and diagnosis among the cases. Furthermore, rs1800797 was also associated with lung cancer among never smokers in the GENEVA dataset. Functional studies identified that the risk allele was associated with increased basal IL-6 mRNA level and greater promoter activity. Furthermore, fibroblasts with the risk allele showed greater induction of IL-6 secretion by hydrogen peroxide or benzo[a]pyrene diolepoxide treatments. CONCLUSIONS: An IL6 promoter variant was associated with lung cancer in uranium miners and never smokers in two external study populations. The associations are strongly supported by the functional relevance that the IL6 promoter SNP affects basal expression and carcinogen-induced IL-6 secretion. CITATION: Leng S, Thomas CL, Snider AM, Picchi MA, Chen W, Willis DG, Carr TG, Krzeminski J, Desai D, Shantu A, Lin Y, Jacobson MR, Belinsky SA. 2016. Radon exposure, IL-6 promoter variants, and lung squamous cell carcinoma in former uranium miners. Environ Health Perspect 124:445-451; http://dx.doi.org/10.1289/ehp.1409437.

Analysis of Genetic Damage in Lymphocytes of Former Uranium Processing Workers.

The frequency of cells containing micronuclei (MN) and the presence of centromeres in these MN were analyzed in lymphocytes of 98 men from Southern Bohemia. Forty-six of them had worked at the uranium processing plant 'MAPE Mydlovary' which was closed in 1991, and 52 men were controls from the same area. FISH using human pan-centromeric chromosome paint was employed to detect centromere-positive (CEN+) and -negative (CEN-) MN. A total of 1,000 binucleated cells (BNC) per participant were analyzed after cytochalasin B treatment. All BNC with MN (CEN+ or CEN-) were recorded. No differences were found between formerly exposed workers and the control group, neither in the total frequency of cells with MN per 1,000 BNC (mean levels ± SD, 9.1 ± 3.1 and 9.8 ± 2.5, respectively) nor in the percentage of CEN- MN, which were equal (50 ± 18 and 49 ± 17, respectively). Also, there was no difference between individuals living in the 3 villages closest to the uranium processing plant and those living further away. Considering the fact that effective doses of the workers at MAPE Mydlovary were overall similar to those of former uranium miners in whom higher frequencies of CEN- MN have been found more than 10 years after they had finished working underground, these results are somewhat surprising. A more detailed analysis of the exposures indicates that uranium miners received a greater percentage of their effective dose from the inhalation of radon and its daughters, whereas uranium processing workers received it from the incorporation of long-lived radioactive nuclides such as uranium. If, as has been suggested before, the higher level of DNA damage in miners is due to induced genomic instability, then this phenomenon may be related to radon exposure rather than exposure to uranium.

Radón y sus efectos en la salud en trabajadores de minas de uranio / Radon and its effects on the health of uranium mine workers

INTRODUCCIÓN: El radón es un gas presente en subsuelo, especialmente en minas de uranio, que produce consecuencias sobre la salud, entre las que destaca el cáncer de pulmón. En EEUU es la segunda causa de mortalidad por esta enfermedad. Pese a la fuerte relación causal no existe normativa específica europea de regulación en mineros. OBJETIVOS: Identificar el efecto del radón y sus derivados sobre la salud de los trabajadores de minas de uranio; describir la asociación entre exposición a radón y a otros minerales sobre la salud y asociación entre radón y consumo de tabaco. METODOLOGÍA: Realizamos una revisión bibliográfica de literatura publicada entre 2007 y 2014, en bases de datos biomédicas, utilizando los criterios de inclusión y exclusión previamente establecidos. RESULTADOS: Se revisan 32 artículos, encontrando un aumento significativo de cáncer pulmonar (SMR-2.03, IC95% 1.96-2.10), incluso a dosis bajas (300-WLM) así como otros cánceres (laringe, gástrico, hepático y leucemia) y enfermedades cerebrovasculares, controlando posibles factores de confusión (tabaco, silicosis, cuarzo y arsénico) no encontrando relación significativa ni sinergias. CONCLUSIÓN: Existe asociación entre la exposición al radón y cáncer pulmonar en minas de uranio, con un periodo medio de latencia de 20 años, determinado por la dosis de radón y el tiempo de exposición. No se ha demostrado riesgo de desarrollar otros tipos de tumores, y los estudios que lo sugieren son poco consistentes

INTRODUCTION: Radon is a gas that can be found underground, particularly in uranium mines, and which has consequences on health, namely lung cancer. It is the second cause of mortality for this disease in the United States. In spite of the strong causal relationship between both elements, there are no specific European regulations concerning miners. OBJECTIVES: To identify the effect of radon and its derivatives on the health of uranium mine workers; to describe the association between exposure to radon and other minerals and health as well as the association between radon and tobacco consumption. METHODS: We perform a bibliographic review of the literature that has been published from 2007 to 2014 in different biomedical databases, using previously established inclusion and exclusion criteria. RESULTS: 32 articles were reviewed and a significant increase of lung cancer was observed (SMR: 2.03, 95% CI: 1.96-2.10) even for low doses (WLM: 300) as well as other types of cancer (laryngeal, gastric and hepatic cancer and leukemia) and cerebrovascular diseases, after adjusting for other confounding factors (tobacco consumption, silicosis, exposure to quartz and arsenic) in which no significant associations or synergies were found. CONCLUSION: There is an association between exposure to radon and lung cancer in uranium mines, with an average latency period of 20 years, determined by the dose of radon and the time of exposure. We did not find risk of developing other types of tumors, and the studies that suggest this hypothesis are inconsistent

Mortality from internal and external radiation exposure in a cohort of male German uranium millers, 1946-2008.

PURPOSE: To examine exposure-response relationships between ionizing radiation and several mortality outcomes in a subgroup of 4,054 men of the German uranium miner cohort study, who worked between 1946 and 1989 in milling facilities, but never underground or in open pit mines. METHODS: Mortality follow-up was from 1946 to 2008, accumulating 158,383 person-years at risk. Cumulative exposure to radon progeny in working level months (WLM) (mean = 8, max = 127), long-lived radionuclides from uranium ore dust in kBqh/m(3) (mean = 3.9, max = 132), external gamma radiation in mSv (mean = 26, max = 667) and silica dust was estimated by a comprehensive job-exposure matrix. Internal Poisson regression models were applied to estimate the linear excess relative risk (ERR) per unit of cumulative exposure. RESULTS: Overall, a total of 457, 717 and 111 deaths occurred from malignant cancer, cardiovascular diseases and non-malignant respiratory diseases, respectively. Uranium ore dust and silica dust were not associated with mortality from any of these disease groups. A statistically significant relationship between cumulative radon exposure and mortality from all cancers (ERR/100 WLM = 1.71; p = 0.02), primarily due to lung cancer (n = 159; ERR/100 WLM = 3.39; p = 0.05), was found. With respect to cumulative external gamma radiation, an excess of mortality of solid cancers (n = 434; ERR/Sv = 1.86; p = 0.06), primarily due to stomach cancer (n = 49, ERR/Sv = 10.0; p = 0.12), was present. CONCLUSION: The present findings show an excess mortality from lung cancer due to radon exposure and from solid cancers due to external gamma radiation in uranium millers that was not statistically significant. Exposure to uranium was not associated with any cause of death, but absorbed organ doses were estimated to be low.

Silica dust, radon and death from non-malignant respiratory diseases in German uranium miners.

OBJECTIVE: To quantify the relationship between death from non-malignant respiratory diseases (NMRD) and exposure to silica dust or radon in a cohort of 58,690 former German uranium miners. METHODS: In the follow-up period from 1946 to 2008, a total of 2336 underlying deaths from NMRDs occurred, including 715 deaths from chronic obstructive pulmonary diseases (COPD) and 975 deaths from silicosis or other pneumoconiosis. Exposure to respirable crystalline silica and radon was individually assessed by means of a comprehensive job-exposure matrix. Risk analyses were based on a linear Poisson regression model with the baseline stratified by age, calendar year and duration of employment. RESULTS: There was no increase in risk of death from COPDs or any other NMRDs in relation to cumulative exposure to silica (mean=5.9, max=56 mg/m(3)-years), except in the group of deaths from silicosis or other pneumoconiosis. Here, a strong non-linear increase in risk was observed. Cumulative radon exposure (mean=280; max=3224 Working Level Months) was not related to death from COPDs or any other NMRDs. CONCLUSIONS: The present findings do not indicate a relationship between mortality from COPD with silica dust or radon. However, validity of cause of death and lack of control for smoking remain potential sources of bias.

Risk of lung cancer from radon exposure: contribution of recently published studies of uranium miners.

The International Commission on Radiological Protection (ICRP) recently estimated the risk of lung cancer associated with radon exposure, and a statement was issued in ICRP Publication 115. This was based on recent epidemiological studies and the results from a joint analysis of cohorts of Czech, French, and German uranium miners, and indicated that the excess relative risk of lung cancer per unit of exposure should be expressed with consideration of chronic exposure over more than 10 years, by modelling time since median exposure, age attained or age at exposure, and taking in account, if possible, interaction between radon and tobacco. The lifetime excess absolute risk (LEAR) calculated from occupational exposure studies is close to 5 × 10(-4) per working level month (WLM) (14 × 10(-5) per hmJ/m(3)). LEAR values estimated using risk models derived from both miners and domestic exposure studies are in good agreement after accounting for factors such as sex, attained age, and exposure scenario. A sensitivity analysis highlighted the high dependence of background mortality rates on LEAR estimates. Using lung cancer rates among Euro-American males instead of the ICRP reference rates (males and females, and Euro-American and Asian populations), the estimated LEAR is close to 7 × 10(-4) per WLM (20 × 10(-5) per hm J/m(3)).

Uranium mining industry views on ICRP statement on radon.

In 2009, the International Commission on Radiological Protection issued a statement on radon which stated that the dose conversion factor for radon progeny would likely double, and the calculation of risk from radon should move to a dosimetric approach, rather than the longstanding epidemiological approach. Through the World Nuclear Association, whose members represent over 90% of the world's uranium production, industry has been examining this issue with a goal of offering expertise and knowledge to assist with the practical implementation of these evolutionary changes to evaluating the risk from radon progeny. Industry supports the continuing use of the most current epidemiological data as a basis for risk calculation, but believes that further examination of these results is needed to better understand the level of conservatism in the potential epidemiological-based risk models. With regard to adoption of the dosimetric approach, industry believes that further work is needed before this is a practical option. In particular, this work should include a clear demonstration of the validation of the dosimetric model which includes how smoking is handled, the establishment of a practical measurement protocol, and the collection of relevant data for modern workplaces. Industry is actively working to address the latter two items.

Effect of site-specific bronchial radon progeny deposition on the spatial and temporal distributions of cellular responses.

Inhaled short-lived radon progenies may deposit in bronchial airways and interact with the epithelium by the emission of alpha particles. Simulation of the related radiobiological effects requires the knowledge of space and time distributions of alpha particle hits and biological endpoints. Present modelling efforts include simulation of radioaerosol deposition patterns in a central bronchial airway bifurcation, modelling of human bronchial epithelium, generation of alpha particle tracks, and computation of spatio-temporal distributions of cell nucleus hits, cell killing and cell transformation events. Simulation results indicate that the preferential radionuclide deposition at carinal ridges plays an important role in the space and time evolution of the biological events. While multiple hits are generally rare for low cumulative exposures, their probability may be quite high at the carinal ridges of the airway bifurcations. Likewise, cell killing and transformation events also occur with higher probability in this area. In the case of uniform surface activities, successive hits as well as cell killing and transformation events within a restricted area (say 0.5 mm(2)) are well separated in time. However, in the case of realistic inhomogeneous deposition, they occur more frequently within the mean cycle time of cells located at the carinal ridge even at low cumulative doses. The site-specificity of radionuclide deposition impacts not only on direct, but also on non-targeted radiobiological effects due to intercellular communication. Incorporation of present results into mechanistic models of carcinogenesis may provide useful information concerning the dose-effect relationship in the low-dose range.

Health effects of uranium: new research findings.

Recent plans for a nuclear renaissance in both established and emerging economies have prompted increased interest in uranium mining. With the potential for more uranium mining worldwide and a growth in the literature on the toxicology and epidemiology of uranium and uranium mining, we found it timely to review the current state of knowledge. Here, we present a review of the health effects of uranium mining, with an emphasis on newer findings (2005-2011). Uranium mining can contaminate air, water, and soil. The chemical toxicity of the metal constitutes the primary environmental health hazard, with the radioactivity of uranium a secondary concern. The update of the toxicologic evidence on uranium adds to the established findings regarding nephrotoxicity, genotoxicity, and developmental defects. Additional novel toxicologic findings, including some at the molecular level, are now emerging that raise the biological plausibility of adverse effects on the brain, on reproduction, including estrogenic effects, on gene expression, and on uranium metabolism. Historically, most epidemiology on uranium mining has focused on mine workers and radon exposure. Although that situation is still overwhelmingly true, a smaller emerging literature has begun to form around environmental exposure in residential areas near uranium mining and processing facilities. We present and critique such studies. Clearly, more epidemiologic research is needed to contribute to causal inference. As much damage is irreversible, and possibly cumulative, present efforts must be vigorous to limit environmental uranium contamination and exposure.

Mortality from circulatory system diseases and low-level radon exposure in the French cohort study of uranium miners, 1946-1999.

OBJECTIVES: The few studies examining the risk of circulatory system diseases (CSD) associated with ionizing radiation have reported inconsistent results. Radon, a known pulmonary carcinogen, emits ionizing radiation. The aim of this study was to examine CSD mortality in a French cohort of uranium miners and evaluate the plausibility of an association with radon exposure. METHODS: The cohort included men employed as uranium miners for >/=1 year between 1946-1990. We obtained vital status and cause of death from national registers and reconstructed radon exposure for each year. Exposure--risk relations were estimated with a linear excess relative risk (ERR) model using a 5-year lag time. RESULTS: The cohort comprised 5086 miners, followed up for a mean duration of 30.1 years. The average cumulative exposure of the radon-exposed miners was 36.6 working level months (WLM). A total of 1411 deaths were observed, including 319 deaths due to CSD. No excess risk was found for this overall cause of death. A significant positive trend was observed between deaths from cerebrovascular diseases (CeVD) and cumulative radon exposure, together with a significant ERR per 100 WLM [ERR per 100 WLM 0.49, 95% confidence interval (95% CI) 0.07-1.23)]. Hard physical activity was identified as a potential modifying factor of the exposure-risk relation. CONCLUSIONS: For the first time in a cohort of uranium miners, our results suggest an association between CeVD mortality and cumulative radon exposure. Due to a lack of data, which limited our ability to assess possible confounding by cardiovascular risk factors, these findings should be interpreted with caution.