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Showing papers in "International Journal of Radiation Biology in 2021"


Journal ArticleDOI
TL;DR: There are well-known correlations between high and moderate doses (>0.5 Gy) of ionizing radiation exposure and circulatory system damage, also between radiation and posterior subcapsular cataract.
Abstract: There are well-known correlations between high and moderate doses (>0.5 Gy) of ionizing radiation exposure and circulatory system damage, also between radiation and posterior subcapsular cataract. ...

40 citations


Journal ArticleDOI
TL;DR: A review of the field of ultra-high dose rates (UHDRs) can be found in this paper, where the authors have developed a multidisciplinary research team focused on investigating the mechanisms and clinical translation of the FLASH effect.
Abstract: A reemergence of research implementing radiation delivery at ultra-high dose rates (UHDRs) has triggered intense interest in the radiation sciences and has opened a new field of investigation in radiobiology. Much of the promise of UHDR irradiation involves the FLASH effect, an in vivo biological response observed to maintain anti-tumor efficacy without the normal tissue complications associated with standard dose rates. The FLASH effect has been validated primarily, using intermediate energy electron beams able to deliver high doses (>7 Gy) in a very short period of time (<200 ms), but has also been found with photon and proton beams. The clinical implications of this new area of research are highly significant, as FLASH radiotherapy (FLASH-RT) has the potential to enhance the therapeutic index, opening new possibilities for eradicating radio-resistant tumors without toxicity. As pioneers in this field, our group has developed a multidisciplinary research team focused on investigating the mechanisms and clinical translation of the FLASH effect. Here, we review the field of UHDR, from the physico-chemical to the biological mechanisms.

36 citations


Journal ArticleDOI
TL;DR: The status of some of the pharmaceuticals currently in late stage development for possible use for individuals unwantedly and acutely injured as a result of radiological/nuclear exposures is reported in this paper.
Abstract: PURPOSE The intent of this article is to report the status of some of the pharmaceuticals currently in late stage development for possible use for individuals unwantedly and acutely injured as a result of radiological/nuclear exposures. The two major questions we attempt to address here are: (a) What medicinals are currently deemed by regulatory authorities (US FDA) to be safe and effective and are being stockpiled? (b) What additional agents might be needed to make the federal/state/local medicinal repositories more robust and useful in effectively managing contingencies involving radiation overexposures? CONCLUSIONS A limited number (precisely four) of medicinals have been deemed safe and effective, and are approved by the US FDA for the 'hematopoietic acute radiation syndrome (H-ARS).' These agents are largely recombinant growth factors (e.g. rhuG-CSF/filgrastim, rhuGM-CSF/sargramostim) that target and stimulate myeloid progenitors within bone marrow. Romiplostim, a small molecular agonist that enhances platelet production via stimulation of bone marrow megakaryocytes, has been recently approved and indicated for H-ARS. It is critical that additional agents for other major sub-syndromes of ARS (gastrointestinal-ARS) be approved. Future success in developing such medicinals will undoubtedly entail some form of a polypharmaceutical strategy, or perhaps novel, bioengineered chimeric agents with multiple, radioprotective/radiomitigative functionalities.

32 citations


Journal ArticleDOI
TL;DR: Niraparib effectively radiosensitizes HNSCCs with a greater benefit seen in HPV(−), and using cell cycle abrogators in combination with PARP inhibitors may be a beneficial treatment option, which emphasizes the importance of HPV status when considering effective treatment strategies.
Abstract: Purpose: Head and neck cancers (HNSCC) are routinely treated with radiotherapy; however, normal tissue toxicity remains a concern. Therefore, it is important to validate treatment modalities combin...

26 citations


Journal ArticleDOI
TL;DR: Protracted low dose and low dose rate neutron exposures impairs executive functions in a high percentage of rats that were normally rested, however further detriments in performance become evident when the rats are subjected to sleep fragmentation.
Abstract: Purpose: Astronauts on the planned missions to Mars are expected to have to work more autonomously than on previous missions. Thus mission success may be influenced by the astronauts' ability to respond quickly to unexpected problems, processes that require several executive functions. The purpose of this study was to determine the impact that prolonged low dose and low dose rate exposure to neutrons had on two executive functions, and whether the severity and incidence of cognitive impairment was altered by sleep fragmentation.Materials and methods: In this study we assessed the impact that prolonged (six month) low dose rate neutron exposure had on the ability of male Wistar rats to perform in two executive function tasks (i.e. attentional set shifting (ATSET) - a constrained cognitive flexibility task and the UCFlex assay - an unconstrained cognitive flexibility task). In recognition of the fact that astronauts also have to contend with inadequate sleep quantity and quality for much of their time in space, we determined the impact that relatively mild sleep disruption had on the ability to perform in the ATSET test in sham and neutron-irradiated rats.Results: Chronic low dose (18 cGy) and dose-rate (1 mGy/day) exposure of rats to mixed neutron and photon over the course of six months resulted in significant impairment of simple discrimination (SD) performance. Should similar effects occur in astronauts subjected to low dose rate exposure to Space Radiation, the impairment of SD performance would result in a decreased ability to identify and learn the 'rules' required to respond to a new task or situation. Analysis of the behavioral data by kernel density estimation revealed that 40% of rats had severe ATSET impairments. This value may be a best-case scenario because exposure to neutrons also adversely impacted performance in the UCFlex task. Furthermore, when the good performing rats were reevaluated after they had been subjected to sleep fragmentation, additional ATSET performance decrements were observed in the set shifting stages of the ATSET test, with only 7.4% of the neutron exposed rats able to successfully perform ATSET under normal and sleep fragmented conditions, as opposed to ∼55% of shams.Conclusion: Protracted low dose and low dose rate neutron exposures impairs executive functions in a high percentage of rats that were normally rested, however further detriments in performance become evident when the rats are subjected to sleep fragmentation.

23 citations


Journal ArticleDOI
TL;DR: The Manhattan Engineering District established a secret laboratory in the mountains of northern New Mexico during World War II (WWII) as mentioned in this paper, where they designed, constructed and tested the first atomi atoms.
Abstract: During World War II (WWII), the Manhattan Engineering District established a secret laboratory in the mountains of northern New Mexico. The mission was to design, construct and test the first atomi...

23 citations


Journal ArticleDOI
TL;DR: In this paper, the effects of UVB and UVA radiation on the Nrf2 signaling pathway in dermal fibroblasts and epidermal keratinocytes and melanocytes are summarized.
Abstract: PURPOSE Excessive exposure of skin to solar radiation is associated with greatly increased production of reactive oxygen and nitrogen species (ROS, RNS) resulting in oxidative stress (OS), inflammation, immunosuppression, the production of matrix metalloproteinase, DNA damage and mutations. These events lead to increased incidence of various skin disorders including photoaing and both non-melanoma and melanoma skin cancers. The ultraviolet (UV) part of sunlight, in particular, is responsible for structural and cellular changes across the different layers of the skin. Among other effects, UV photons stimulate oxidative damage to biomolecules via the generation of unstable and highly reactive compounds. In response to oxidative damage, cytoprotective pathways are triggered. One of these is the pathway driven by the nuclear factor erythroid-2 related factor 2 (Nrf2). This transcription factor translocates to the nucleus and drives the expression of numerous genes, among them various detoxifying and antioxidant enzymes. Several studies concerning the effects of UV radiation on Nrf2 activation have been published, but different UV wavelengths, skin cells or tissues and incubation periods were used in the experiments that complicate the evaluation of UV radiation effects. CONCLUSIONS This review summarizes the effects of UVB (280-315 nm) and UVA (315-400 nm) radiation on the Nrf2 signaling pathway in dermal fibroblasts and epidermal keratinocytes and melanocytes. The effects of natural compounds (pure compounds or mixtures) on Nrf2 activation and level as well as on Nrf2-driven genes in UV irradiated human skin fibroblasts, keratinocytes and melanocytes are briefly mentioned as well.HighlightsUVB radiation is a rather poor activator of the Nrf2-driven pathway in fibroblastsUVA radiation stimulates Nrf2 activation in dermal fibroblastsEffects of UVA on the Nrf2 pathway in keratinocytes and melanocytes remain unclearLong-term Nrf2 activation in keratinocytes disturbs their normal differentiationPharmacological activation of Nrf2 in the skin needs to be performed carefully.

23 citations


Journal ArticleDOI
TL;DR: The projected existence and magnitude of carcinogenic effects of ionizing radiation at low doses and lowdose rates is perhaps the most important issue in radiation protection today as mentioned in this paper, and studies of chi...
Abstract: The projected existence and magnitude of carcinogenic effects of ionizing radiation at low doses and low-dose rates is perhaps the most important issue in radiation protection today. Studies of chi...

20 citations


Journal ArticleDOI
TL;DR: It is anticipated that AOPs could be adopted as a method to synthesize current available information to facilitate the identification of knowledge gaps, better co-ordinate research and qualitatively and quantitatively link key events to an adverse outcome.
Abstract: Background: A large body of radiobiological data has been generated over the past century using in vitro, animal and epidemiological models. This information represents global efforts to understand...

19 citations


Journal ArticleDOI
TL;DR: This AOP defines a classic targeted response to a radiation insult with an AO of lung cancer that is relevant to radon gas exposure and is an example of how the AOP methodology can be applied to sources of radiation to help support areas of risk assessment.
Abstract: Background: Adverse outcome pathways (AOPs) describe how a measurable sequence of key events, beginning from a molecular initiator, can lead to an adverse outcome of relevance to risk assessment. A...

19 citations


Journal ArticleDOI
TL;DR: A facility to perform high LET studies in mice and rats at space relevant dose rates and career-relevant doses using neutrons emitted from the spontaneous fission of 252Cf is developed.
Abstract: PURPOSE During extended missions into deep space, astronauts will be exposed to a complex radiation field that includes high linear energy transfer (LET) radiation from high energy, heavy ions (HZE particles) at low dose rates of about 0.5 mGy/d for long durations. About 20% of the dose is delivered by ions with LET greater than 10 keV/µm. There are sparse empirical data in any species for carcinogenic effects from whole-body exposures to external sources of mixed or high LET radiation at this level of dose rates. For the induction of solid tumors, acute exposures to HZE ions have been shown to be substantially more effective per unit dose than low LET exposures associated with photons. To determine the health effects of high LET radiation at space-relevant dose rates on experimental animals, we developed a vivarium in which rodents could be irradiated with Californium (252Cf) neutrons for protracted periods of time. MATERIALS AND METHODS The neutron source is a panoramic irradiator containing 252Cf located in a concrete shielded vault with a footprint of 53 m2. The vault can accommodate sufficient caging to simultaneously irradiate 900 mice and 60 rats for durations up to 400 d at a dose rate of 1 mGy/d and is approved for extended animal husbandry. RESULTS The mixed field fluence is a combination of neutrons and photons emitted directly from the source and scattered particles from the concrete walls and floor. Mixed field dosimetry was performed using a miniature GM counter and CaF2:Dy thermoluminescent dosimeters (TLD) for photons and tissue-equivalent proportional counters (TEPC) for neutrons. TEPC data provided macroscopic dose rates as well as measurements of radiation quality based on lineal energy, y, and LET. The instantaneous dose rate from the source decreases with a half-life of 2.6 years. The exposure time is adjusted weekly to yield a total dose 1 mGy/d. The photon contribution is 20% of the total dose. The uncertainty in the delivered dose is estimated to be ±20% taking into account spatial variations in the room and random position of mice in each cage. The dose averaged LET for the charged particle recoil nuclei is 68 keV/µ. CONCLUSIONS We have developed a facility to perform high LET studies in mice and rats at space relevant dose rates and career-relevant doses using neutrons emitted from the spontaneous fission of 252Cf.

Journal ArticleDOI
TL;DR: A RT dose ≤0.5 Gy provides an acceptable LAR estimate (≤1%) for RIC and REID, irrespective of sex and age.
Abstract: Recently, low dose radiotherapy delivered to the whole lung has been proposed as treatment for the pneumonia due to COVID-19. Although there is biological plausibility for its use, the evidence sup...

Journal ArticleDOI
TL;DR: The Million Person Study (MPS) of U.S. Radiation Workers and Veterans was designed to examine health effects following chronic exposures in contrast with brief exposures as experienced by the Japanese atomic bomb survivors.
Abstract: Background Epidemiologic studies of radiation-exposed populations form the basis for human safety standards. They also help shape public health policy and evidence-based health practices by identifying and quantifying health risks of exposure in defined populations. For more than a century, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels delivered at a low-dose rate remain equivocal. Materials and methods The Million Person Study (MPS) of U.S. Radiation Workers and Veterans was designed to examine health effects following chronic exposures in contrast with brief exposures as experienced by the Japanese atomic bomb survivors. Radiation associations for rare cancers, intakes of radionuclides, and differences between men and women are being evaluated, as well as noncancers such as cardiovascular disease and conditions such as dementia and cognitive function. The first international symposium, held November 6, 2020, provided a broad overview of the MPS. Representatives from four U.S. government agencies addressed the importance of this research for their respective missions: U.S. Department of Energy (DOE), the Centers for Disease Control and Prevention (CDC), the U.S. Department of Defense (DOD), and the National Aeronautical Space Agency (NASA). The major components of the MPS were discussed and recent findings summarized. The importance of radiation dosimetry, an essential feature of each MPS investigation, was emphasized. Results The seven components of the MPS are DOE workers, nuclear weapons test participants, nuclear power plant workers, industrial radiographers, medical radiation workers, nuclear submariners, other U.S. Navy personnel, and radium dial painters. The MPS cohorts include tens of thousands of workers with elevated intakes of alpha particle emitters for which organ-specific doses are determined. Findings to date for chronic radiation exposure suggest that leukemia risk is lower than after acute exposure; lung cancer risk is much lower and there is little difference in risks between men and women; an increase in ischemic heart disease is yet to be seen; esophageal cancer is frequently elevated but not myelodysplastic syndrome; and Parkinson's disease may be associated with radiation exposure. Conclusions The MPS has provided provocative insights into the possible range of health effects following low-level chronic radiation exposure. When the 34 MPS cohorts are completed and combined, a powerful evaluation of radiation-effects will be possible. This final article in the MPS special issue summarizes the findings to date and the possibilities for the future. A National Center for Radiation Epidemiology and Biology is envisioned.

Journal ArticleDOI
TL;DR: In this article, the impacts of various types of environmental occupational and medical stressors on human health have been investigated and a vast amount of data across many scientific disciplines has been produced.
Abstract: Decades of research to understand the impacts of various types of environmental occupational and medical stressors on human health have produced a vast amount of data across many scientific discipl...

Journal ArticleDOI
TL;DR: Transcriptomic-based approaches are being developed to meet the needs for large-scale radiation dose and injury assessment and provide population triage following a radiological or nuclear event as mentioned in this paper.
Abstract: Transcriptomic-based approaches are being developed to meet the needs for large-scale radiation dose and injury assessment and provide population triage following a radiological or nuclear event. T...

Journal ArticleDOI
TL;DR: In this article, the importance of hypoxia to radiotherapy with a particular focus on immune responses, metastatic potential and FLASH radiotherapy is discussed. But, the authors do not consider the effects of hypoxygenation on normal tissue.
Abstract: Purpose: Hypoxia (low oxygen) is a common feature of solid tumours that has been intensely studied for more than six decades. Here we review the importance of hypoxia to radiotherapy with a particular focus on the contribution of hypoxia to immune responses, metastatic potential and FLASH radiotherapy, active areas of research by leading women in the field. Conclusion: Although hypoxia-driven metastasis and immunosuppression can negatively impact clinical outcome, understanding these processes can also provide tumour-specific vulnerabilities that may be therapeutically exploited. The different oxygen tensions present in tumours and normal tissues may underpin the beneficial FLASH sparing effect seen in normal tissue and represents a perfect example of advances in the field that can leverage tumour hypoxia to improve future radiotherapy treatments.

Journal ArticleDOI
TL;DR: The adverse outcome pathway (AOP) approach was used with consultation from field experts to delineate connectivities of events specifically to cardiovascular disease (CVD) initiation and progression, and the questions and discussions needed to develop an AOP for CVD resulting from ionizing radiation (IR) exposure.
Abstract: Background The circulatory system distributes nutrients, signaling molecules, and immune cells to vital organs and soft tissues. Epidemiological, animal, and in vitro cellular mechanistic studies have highlighted that exposure to ionizing radiation (IR) can induce molecular changes in cellular and subcellular milieus leading to long-term health impacts, particularly on the circulatory system. Although the mechanisms for the pathologies are not fully elucidated, endothelial dysfunction is proven to be a critical event via radiation-induced oxidative stress mediators. To delineate connectivities of events specifically to cardiovascular disease (CVD) initiation and progression, the adverse outcome pathway (AOP) approach was used with consultation from field experts. AOPs are a means to organize information around a disease of interest to a regulatory question. An AOP begins with a molecular initiating event and ends in an adverse outcome via sequential linkages of key event relationships that are supported by evidence in the form of the modified Bradford-Hill criteria. Detailed guidelines on building AOPs are provided by the Organisation for Economic Cooperation and Development (OECD) AOP program. Here, we report on the questions and discussions needed to develop an AOP for CVD resulting from IR exposure. A recent workshop jointly organized by the MELODI (Multidisciplinary European Low Dose Initiative) and the ALLIANCE (European Radioecology Alliance) associations brought together experts from the OECD to present the AOP approach and tools with examples from the toxicology field. As part of this workshop, four working groups were formed to discuss the identification of adverse outcomes relevant to radiation exposures and development of potential AOPs, one of which was focused on IR-induced cardiovascular effects. Each working group comprised subject matter experts and radiation researchers interested in the specific disease area and included an AOP coach. Conclusion The CVD working group identified the critical questions of interest for AOP development, including the exposure scenario that would inform the evidence, the mechanisms of toxicity, the initiating event, intermediate key events/relationships, and the type of data currently available. This commentary describes the four-day discussion of the CVD working group, its outcomes, and demonstrates how collaboration and expert consultation is vital to informing AOP construction.

Journal ArticleDOI
TL;DR: The findings demonstrate that Regorafenib enhanced radiosensitivity of breast cancer cells by inhibiting the expression of multiple receptor tyrosine kinases, VEGF-mediated angiogenesis and DNA damage response in TNBC.
Abstract: Purpose: Triple-negative breast cancer (TNBC) is the most challenging and aggressive subtype of breast cancer with limited treatment options because of tumor heterogeneity, lack of druggable target...

Journal ArticleDOI
TL;DR: In this article, the dicentric chromosome assay (DCA) results were homogeneous between participants and matched well with the reference doses (≥95% of estimates within ± 0.5 Gy of the reference).
Abstract: PURPOSE Biological and/or physical assays for retrospective dosimetry are valuable tools to recover the exposure situation and to aid medical decision making. To further validate and improve such biological and physical assays, in 2019, EURADOS Working Group 10 and RENEB performed a field exercise in Lund, Sweden, to simulate various real-life exposure scenarios. MATERIALS AND METHODS For the dicentric chromosome assay (DCA), blood tubes were located at anthropomorphic phantoms positioned in different geometries and were irradiated with a 1.36 TBq 192Ir-source. For each exposure condition, dose estimates were provided by at least one laboratory and for four conditions by 17 participating RENEB laboratories. Three radio-photoluminescence glass dosimeters were placed at each tube to assess reference doses. RESULTS The DCA results were homogeneous between participants and matched well with the reference doses (≥95% of estimates within ±0.5 Gy of the reference). For samples close to the source systematic underestimation could be corrected by accounting for exposure time. Heterogeneity within and between tubes was detected for reference doses as well as for DCA doses estimates. CONCLUSIONS The participants were able to successfully estimate the doses and to provide important information on the exposure scenarios under conditions closely resembling a real-life situation.

Journal ArticleDOI
TL;DR: In a nuclear or radiological event, an early diagnostic tool is needed to distinguish the worried well from those individuals who may later develop life-threatenFing hematologic acute radiation syn...
Abstract: In a nuclear or radiological event, an early diagnostic tool is needed to distinguish the worried well from those individuals who may later develop life-threatenFing hematologic acute radiation syn...

Journal ArticleDOI
TL;DR: A high-level review of a recent report developed by a Committee for the National Council on Radiation Protection and Measurements titled ‘Approaches for Integrating Information from Radiation Biology and Epidemiology to Enhance Low-Dose Health Risk Assessment’, which provides the case for integrating data from radiation biology studies with epidemiological studies to develop Biologically-Based Dose-Response (BBDR) models.
Abstract: The overall aim of this contribution to the ‘Second Bill Morgan Memorial Special Issue’ is to provide a high-level review of a recent report developed by a Committee for the National Council on Rad...

Journal ArticleDOI
TL;DR: This review focuses on potentially novel mechanisms of TTFields anti-tumor action and their implications in completed and ongoing clinical trials and pre-clinical studies, and discusses advantages and strategies using chemotherapy agents and radiation therapy in combination with TTF yields for future clinical use.
Abstract: Traditional cancer therapy choices for clinicians are surgery, chemotherapy, radiation and immune therapy which are used either standalone therapies or in various combinations. Other physical modal...

Journal ArticleDOI
TL;DR: For 65 years, the interpretation of the statistical association between the risk of cancer in a child and a prior diagnostic X-ray examination of the abdomen of the pregnant mother has been debated.
Abstract: For 65 years the interpretation of the statistical association between the risk of cancer in a child and a prior diagnostic X-ray examination of the abdomen of the pregnant mother has been debated

Journal ArticleDOI
TL;DR: In this paper, the authors present an inter-laboratory comparison (ILC) of biological dosimetry networks in case of a mass-casualty radiological event.
Abstract: Purpose In case of a mass-casualty radiological event, there would be a need for networking to overcome surge limitations and to quickly obtain homogeneous results (reported aberration frequencies or estimated doses) among biodosimetry laboratories. These results must be consistent within such network. Inter-laboratory comparisons (ILCs) are widely accepted to achieve this homogeneity. At the European level, a great effort has been made to harmonize biological dosimetry laboratories, notably during the MULTIBIODOSE and RENEB projects. In order to continue the harmonization efforts, the RENEB consortium launched this intercomparison which is larger than the RENEB network, as it involves 38 laboratories from 21 countries. In this ILC all steps of the process were monitored, from blood shipment to dose estimation. This exercise also aimed to evaluate the statistical tools used to compare laboratory performance. Materials and methods Blood samples were irradiated at three different doses, 1.8, 0.4 and 0 Gy (samples A, C and B) with 4-MV X-rays at 0.5 Gy min-1, and sent to the participant laboratories. Each laboratory was requested to blindly analyze 500 cells per sample and to report the observed frequency of dicentric chromosomes per metaphase and the corresponding estimated dose. Results This ILC demonstrates that blood samples can be successfully distributed among laboratories worldwide to perform biological dosimetry in case of a mass casualty event. Having achieved a substantial harmonization in multiple areas among the RENEB laboratories issues were identified with the available statistical tools, which are not capable to advantageously exploit the richness of results of a large ILCs. Even though Z- and U-tests are accepted methods for biodosimetry ILCs, setting the number of analyzed metaphases to 500 and establishing a tests' common threshold for all studied doses is inappropriate for evaluating laboratory performance. Another problem highlighted by this ILC is the issue of the dose-effect curve diversity. It clearly appears that, despite the initial advantage of including the scoring specificities of each laboratory, the lack of defined criteria for assessing the robustness of each laboratory's curve is a disadvantage for the 'one curve per laboratory' model. Conclusions Based on our study, it seems relevant to develop tools better adapted to the collection and processing of results produced by the participant laboratories. We are confident that, after an initial harmonization phase reached by the RENEB laboratories, a new step toward a better optimization of the laboratory networks in biological dosimetry and associated ILC is on the way.

Journal ArticleDOI
TL;DR: In this article, the authors reviewed recent researches about cardiac toxicity of radiotherapy in clinical characteristics, mechanisms, diagnosis, and prevention, and concluded that early diagnosis and interventions for the prevention of RIHD are crucial.
Abstract: PURPOSE Radiation-induced heart disease (RIHD) is one of the most serious complications of radiotherapy. The purpose of this paper is to review recent researches about cardiac toxicity of radiotherapy in clinical characteristics, mechanisms, diagnosis, and prevention. CONCLUSIONS Powered by the rapid development of medicine, the overall survival (OS) of cancer has been improved significantly. Surgery, chemotherapy, and radiotherapy (RT) are three critical ways in the comprehensive treatments of cancer. There is a consensus that early diagnosis and interventions for the prevention of RIHD are crucial. This review concludes recent clinical and experimental studies on RIHD. RIHD, a heterogeneous and serious disease, is a spectrum of heart disease including myocardial disease, pericarditis, coronary artery disease, valvular heart disease, and conduction system dysfunction. Mean heart dose, biomarkers, and detecting techniques are important components in detecting heart injury. Improvements in radiotherapy regimens remain the primary goal of prevention. Further investigation is needed beyond the observation period of most of these studies.

Journal ArticleDOI
TL;DR: In this article, the authors examined the level of radiation risk for chronic exposures received gradually over time and not acutely as was the case for the Japanese atomic bomb survivors, and found that exposure to radiation increased the risk of leukemia other than chronic lymphocytic leukemia (CLL), 3,382 from lung cancer, 140 from Parkinson's disease and 5,410 from IHD.
Abstract: Background The aim of the Million Person Study (MPS) of Low Dose Health Effects is to examine the level of radiation risk for chronic exposures received gradually over time and not acutely as was the case for the Japanese atomic bomb survivors. Nuclear power plant (NPP) workers comprise nearly 15 percent of the MPS. Leukemia, selected cancers, Parkinson's disease, ischemic heart disease (IHD) and other causes of death are evaluated. Methods and material The U.S. Nuclear Regulatory Commission's Radiation Exposure Information and Reporting System (REIRS) and the Landauer, Inc. dosimetry databases identified 135,193 NPP workers first monitored 1957-1984. Annual personal dose equivalents [Hp(10)] were available for each worker. Radiation records from all places of employment were sought. Vital status was determined through 2011. Mean absorbed doses to red bone marrow (RBM), esophagus, lung, colon, brain and heart were estimated by adjusting the recorded Hp(10) for each worker by scaling factors, accounting for exposure geometry and energy of the incident gamma radiation. Standardized mortality ratios (SMR) were calculated. Radiation risks were estimated using Cox proportional hazards models. Results Nearly 50% of workers were employed for more than 20 years. The mean duration of follow-up was 30.2 y. Overall, 29,076 total deaths occurred, 296 from leukemia other than chronic lymphocytic leukemia (CLL), 3,382 from lung cancer, 140 from Parkinson's disease and 5,410 from IHD. The mean dose to RBM was 37.9 mGy (maximum 1.0 Gy; percent >100 mGy was 9.2%), 43.2 mGy to lung, 43.7 mGy to colon, 33.2 mGy to brain, and 43.9 mGy to heart. The SMRs (95% CI) were 1.06 (0.94;1.19) for leukemia other than CLL, 1.10 (1.07;1.14) for lung cancer, 0.90 (0.76;1.06) for Parkinson's disease, and 0.80 (0.78; 0.82) for IHD. The excess relative risk (ERR) per 100 mGy for leukemia other than CLL was 0.15 (90% CI 0.001; 0.31). For all solid cancers the ERR per 100 mGy (95% CI) was 0.01 (-0.03; 0.05), for lung cancer -0.04 (-0.11; 0.02), for Parkinson's disease 0.24 (-0.02; 0.50), and for IHD -0.01 (-0.06; 0.04). Conclusion Prolonged exposure to radiation increased the risk of leukemia other than CLL among NPP workers. There was little evidence for a radiation-association for all solid cancers, lung cancer or ischemic heart disease. Increased precision will be forthcoming as the different cohorts within the MPS are combined, such as industrial radiographers and medical radiation workers who were assembled and evaluated in like manner.

Journal ArticleDOI
TL;DR: In this paper, the authors used Cox proportional hazards models to estimate organ-specific radiation risks for medical radiation workers, including lung cancer, leukemia, ischemic heart disease, and other causes of death.
Abstract: Background Estimates of radiation risks following prolonged exposures at low doses and low-dose rates are uncertain. Medical radiation workers are a major component of the Million Person Study (MPS) of low-dose health effects. Annual personal dose equivalents, HP(10), for individual workers are available to facilitate dose-response analyses for lung cancer, leukemia, ischemic heart disease (IHD) and other causes of death. Materials and methods The Landauer, Inc. dosimetry database identified 109,019 medical and associated radiation workers first monitored 1965-1994. Vital status and cause of death were determined through 2016. Mean absorbed doses to red bone marrow (RBM), lung, heart, and other organs were estimated by adjusting the recorded HP(10) for each worker by scaling factors, accounting for exposure geometry, energy of the incident photon radiation, sex of the worker and whether an apron was worn. There were 4 exposure scenarios: general radiology characterized by low-energy x-ray exposure with no lead apron use, interventional radiologists/cardiologists who wore aprons, nuclear medicine personnel and radiation oncologists exposed to high-energy photon radiation, and other workers. Standardized mortality ratio (SMR) analyses were performed. Cox proportional hazards models were used to estimate organ-specific radiation risks. Results Overall, 11,433 deaths occurred (SMR 0.60; 95%CI 0.59,0.61), 126 from leukemia other than chronic lymphocytic leukemia (CLL), 850 from lung cancer, and 1,654 from IHD. The mean duration of monitoring was 23.7 y. The excess relative rate (ERR) per 100 mGy was estimated as 0.10 (95% CI -0.34, 0.54) for leukemia other than CLL, 0.15 (0.02, 0.27) for lung cancer, and -0.10 (-0.27, 0.06) for IHD. The ERR for lung cancer was 0.16 (0.01, 0.32) among the 55,218 male workers and 0.09 (-0.19, 0.36) among the 53,801 female workers; a difference that was not statistically significant (p value =0.062). Conclusions Medical radiation workers were at increased risk for lung cancer that was higher among men than women, although this difference was not statistically significant. In contrast, the study of Japanese atomic bomb survivors exposed briefly to radiation in 1945 found females to be nearly 3 times the radiation risk of lung cancer compared with males on a relative scale. For medical workers, there no statistically significant radiation-associations with leukemia excluding CLL, IHD or other specific causes of death. Combining these data with other cohorts within the MPS, such as nuclear power plant workers and industrial radiographers, will enable more precise estimates of radiation risks at relatively low cumulative doses.

Journal ArticleDOI
TL;DR: A better consolidation of mechanistic research may serve to guide priority research and facilitate translation to risk assessment in the radiation field, and allow for improved linkage of mechanism data to human relevance and better support radiation risk assessments.
Abstract: Disease prevention and prediction have led to the generation of phenotypically based methods for deriving the limits of safety across toxicological disciplines. In the ionizing radiation field, hum...

Journal ArticleDOI
TL;DR: The WEE1, CHK1, and ATR kinases are key factors in cell cycle checkpoint regulation and are essential for checkpoint regulation as discussed by the authors, however, they are not essential for activation.
Abstract: Radiation-induced activation of cell cycle checkpoints have been of long-standing interest. The WEE1, CHK1 and ATR kinases are key factors in cell cycle checkpoint regulation and are essential for ...

Journal ArticleDOI
TL;DR: In this paper, the authors conducted a systematic review on the use of low-dose radiotherapy (LD-RT) in the management of various inflammatory disorders, including osteoarthritis.
Abstract: Background Osteoarthritis (OA), the most common degenerative joint disease, is associated with severe functional limitation and impairment of quality of life. Numerous reports have documented the clinical efficacy of low-dose radiotherapy (LD-RT) in the management of various inflammatory disorders, including OA. In this paper, we assessed the clinical literature involving the use of LD-RT in the treatment of OA, its dose-response features, possible underlying mechanistic features, and optimal therapeutic dose range. Methods We carried out a systematic review based on the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements and evaluated articles meeting the inclusion criteria for this review. Results A total of 361 articles were identified from databases, such as Scopus, PubMed, Embase, and Science Direct out of which 224 articles were duplicates and were discarded. Of the remaining 137 articles, 74 articles were un-related, 27 articles were review articles, eight were conference abstracts, three were letters, two were editorials, two were notes, and one was a book chapter. Finally, 20 articles met all the inclusion criteria and were included in this systematic review. Discussion Several single-arm retrospective/prospective studies showed advantages for LD-RT in the management of OA in terms of pain relief, improvement of mobility and function, and showed minimal side effects. Mechanistic considerations involve positive subcellular effects mediated by the activation of a nuclear factor erythroid 2-related transcription factor (Nrf2) mediated antioxidant response. Further research on both the short- and long-term effects of LD-RT on OA and other inflammatory disorders is recommended.