Purpose: Routine dental X-rays are among the most common sources of ionizing radiation exposure for healthy individuals globally, with 300 examinations/1000 individuals/year as documented by the ...United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) global survey of medical radiation usage and exposure. Furthermore, in the United States of America, an increased use of dental radiography is evident. However, with the shift from using film to digital image receptors, the dose of radiation per routine examination has decreased. Despite this, there remains public concern of dental X-rays. This continuing concern highlights the need to review the literature on biological and health effects related to exposure, from dental X-rays.
Material and methods: This report presents studies investigating biological and health effects related to exposures using dental X-rays in patients and provides a critical evaluation. Relevant studies specific to dental X-rays are reviewed from 1970 and onward with the bulk data in this field resulting from epidemiological and biomonitoring studies.
Results: While, most epidemiological studies suggest a possible correlation between head/neck related tumors and exposure to dental X-rays, evidence for causation is lacking. Biomonitoring studies suggest that exposure to low-level radiation such as that of dental radiography may not be a factor in inducing long-term chromosomal damage, but may result in localized cytotoxicity in the irradiated region of the mouth, with no long-term harm.
Conclusions: In general, the total number of studies is low and the majority of the data has been generated from poorly designed experiments. This review will highlight shortcomings that could influence outcomes and provide a more balanced interpretation that could impact the public perception and the level of public concern on the health effects resulting from dental X-rays.
In the event of a widespread radiological incident, thousands of individuals will require rapid assessment of exposure using validated biodosimetry assays to inform clinical triage. In this scenario, ...multiple biodosimetry laboratories may be necessary for large-volume sample processing. To meet this need, we have developed a high-throughput assay for the rapid measurement of intracellular protein biomarkers in human peripheral blood samples using an Imaging Flow Cytometry (IFC) platform. The objective of this work was to harmonize and validate the reproducibility of our blood biomarker assay for radiation exposure across three IFC instruments, two located at Columbia University (CU) and the third at Health Canada. The Center for Radiological Research (CRR) at CU served as the central laboratory and reference instrument, where samples were prepared in triplicate, labeled with two radiation responsive leukocyte biomarkers (BAX and phosphor-p53 (Ser37)), and distributed for simultaneous interrogation by each IFC. Initial tests showed that significantly different baseline biomarker measurements were generated on each instrument when using the same acquisition settings, suggesting that harmonization of signal intensities is necessary. Subsequent tests harmonized biomarker measurements after irradiation by modulating laser intensity using two reference materials: unstained samples and standardized rainbow beads. Both methods generated measurements on each instrument without significant differences between the new and references instruments, allowing for the use of one master template to quantify biomarker expression across multiple instruments. Deming regression analyses of 0-5 Gy dose-response curves showed overall good correlation of BAX and p53 values across new and reference instruments. While Bland-Altman analyses indicated low to moderate instrument biases, ROC Curve analyses ultimately show successful discrimination between exposed and unexposed samples on each instrument (AUC values > 0.85).
Abstract
The dicentric chromosome assay (DCA) is a well-established biodosimetry test to estimate exposure to ionizing radiation. The Korea Institute of Radiological and Medical Sciences (KIRAMS) ...established a DCA protocol as a medical response to radiation emergencies in South Korea. To maintain its accuracy and performance, intercomparison exercises with Health Canada (HC) have been conducted; herein, we aimed to validate our capacity of DCA analysis based on those results. Blood samples irradiated at HC were shipped to KIRAMS to assess the irradiation dose to blinded samples using conventional DCA full scoring and triage-based techniques (conventional DCA scoring in triage mode and DCA QuickScan method). Actual doses fell within the 95% confidence intervals of dose estimates for 70–100% of the blinded samples in 2015–2018. All methods discriminated binary dose categories, reflecting clinical significance. This DCA can be used as a reliable radiation biodosimetry tool in preparation for radiation accidents in South Korea.
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.
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.
The dose of ionizing radiation received by an individual can be determined using biodosimetry methods which measure biomarkers of exposure in tissue samples from that individual. These markers can be ...expressed in many ways, including DNA damage and repair processes. Following a mass casualty event involving radiological or nuclear material, it is important to rapidly provide this information to medical responders to assist in the medical management of potentially exposed casualties. Traditional methods of biodosimetry rely on microscope analysis, making them time-consuming and labor-intensive. To increase sample throughput following a large-scale radiological mass casualty event, several biodosimetry assays have been adapted for analysis by imaging flow cytometry. This chapter briefly reviews these methods with a focus on the most current methodology to identify and quantify micronuclei in binucleated cells within the cytokinesis-block micronucleus assay using an imaging flow cytometer.
Adverse outcome pathways (AOPs) provide a modular framework for describing sequences of biological key events (KEs) and key event relationships (KERs) across levels of biological organization. ...Empirical evidence across KERs can support construction of quantified AOPs (qAOPs). Using an example AOP of energy deposition from ionizing radiation onto DNA leading to lung cancer incidence, we investigate the feasibility of quantifying data from KERs supported by all types of stressors. The merits and challenges of this process in the context of AOP construction are discussed.
Empirical evidence across studies of dose-response from four KERs of the AOP were compiled independently for quantification. Three upstream KERs comprised of evidence from various radiation types in line with AOP guidelines. For these three KERs, a focused analysis of data from alpha-particle studies was undertaken to better characterize the process to the adverse outcome (AO) for a radon gas stressor. Numerical information was extracted from tables and graphs to plot and tabulate the response of KEs. To complement areas of the AOP quantification process, Monte Carlo (MC) simulations in TOPAS-nBio were performed to model exposure conditions relevant to the AO for an example bronchial compartment of the lung with secretory cell nuclei targets.
Quantification of AOP KERs highlighted the relevance of radiation types under the stressor-agnostic intent of AOP design, motivating a focus on specific types. For a given type, significant differences of KE response indicate meaningful data to derive linkages from the MIE to the AO is lacking and that better response-response focused studies are required. The MC study estimates the linear energy transfer (LET) of alpha-particles emitted by radon-222 and its progeny in the secretory cell nuclei of the example lung compartment to range from
to
keV/µm.
Quantifying AOP components provides a means to assemble empirical evidence across different studies. This highlights challenges in the context of studies examining similar endpoints using different radiation types. Data linking KERs to a MIE of 'deposition of energy' is shown to be non-compatible with the stressor-agnostic principles of AOP design. Limiting data to that describing response-response relationships between adjacent KERs may better delineate studies relevant to the damage that drives a pathway to the next KE and still support an 'all hazards' approach. Such data remains limited and future investigations in the radiation field may consider this approach when designing experiments and reporting their results and outcomes.
Abstract
Biomarkers for ionising radiation exposure have great utility in scenarios where there has been a potential exposure and physical dosimetry is missing or in dispute, such as for occupational ...and accidental exposures. Biomarkers that respond as a function of dose are particularly useful as biodosemeters to determine the dose of radiation to which an individual has been exposed. These dose measurements can also be used in medical scenarios to track doses from medical exposures and even have the potential to identify an individual’s response to radiation exposure that could help tailor treatments. The measurement of biomarkers of exposure in medicine and for accidents, where a larger number of samples would be required, is limited by the throughput of analysis (i.e. the number of samples that could be processed and analysed), particularly for microscope-based methods, which tend to be labour-intensive. Rapid analysis in an emergency scenario, such as a large-scale accident, would provide dose estimates to medical practitioners, allowing timely administration of the appropriate medical countermeasures to help mitigate the effects of radiation exposure. In order to improve sample throughput for biomarker analysis, much effort has been devoted to automating the process from sample preparation through automated image analysis. This paper will focus mainly on biological endpoints traditionally analysed by microscopy, specifically dicentric chromosomes, micronuclei and gamma-H2AX. These endpoints provide examples where sample throughput has been improved through automated image acquisition, analysis of images acquired by microscopy, as well as methods that have been developed for analysis using imaging flow cytometry.
Purpose: Based on the experience of biodosimetry laboratories during the COVID-19 pandemic, the purpose of this paper is to describe the challenges of providing biodosimetry service in the event of a ...major radiation incident during a pandemic. This includes describing some of the preparations and planning made by biodosimetry laboratories and special challenges in maintaining a state of readiness while adhering to safety protocols and balancing the need to assist with the COVID-19 response where possible. Experiences of several biodosimetry laboratories will be described and lessons learned will be outlined that could be applied to any large population-scale emergencies.Conclusions: There are many challenges that arise when maintaining capacity and capabilities for biodosimetry when faced with a global pandemic such as COVID-19. The key is to be prepared for anything within reason. This includes, but is not limited to, maintaining flexibility, shifting and reorganizing deployment of staff between pandemic response and biodosimetry needs, strengthening networks to be able to provide assistance to other laboratories, managing staff in the face of possible infections and preparing protocols for the handling of potentially infected biological samples according to regulatory requirements. By implementing these recommendations, international biodosimetry networks can be prepared to address large-scale radiological incidents within the context of a pandemic and ensure the safety of biodosimetry personnel as well as victims in such dual emergencies.
Objet : Sur la base de l'expérience des laboratoires de biodosimétrie au cours de la pandémie COVID-19, l'objet de ce document est de décrire les défis liés à la fourniture d'un service de biodosimétrie en cas d'incident radiologique majeur au cours d'une pandémie. Il s'agit notamment de décrire certains des préparatifs et de la planification effectués par les laboratoires de biodosimétrie, ainsi que les difficultés particulières liées au maintien d'un état de préparation tout en respectant les protocoles de sécurité et en conciliant la nécessité de participer à la réponse à la pandémie COVID-19, dans la mesure du possible. L'expérience de plusieurs laboratoires de biodosimétrie sera décrite et les enseignements tirés pourront être appliqués à toute situation d'urgence touchant une population importante.Conclusions : Le maintien des capacités et des compétences en biodosimétrie face à une pandémie mondiale telle que COVID-19 pose de nombreux défis. L'essentiel est d'être prêt à tout, dans la limite du raisonnable. Il s'agit notamment de maintenir la flexibilité, de déplacer et de réorganiser le déploiement du personnel entre la réponse à la pandémie et les besoins en biodosimétrie, de renforcer les réseaux afin de pouvoir fournir une assistance à d'autres laboratoires, de gérer le personnel face à d'éventuelles infections et de préparer des protocoles pour la manipulation d'échantillons biologiques potentiellement infectés, conformément aux exigences réglementaires. En mettant en œuvre ces recommandations, les réseaux internationaux de biodosimétrie peuvent être préparés à faire face à des incidents radiologiques de grande ampleur dans le contexte d'une pandémie et à assurer la sécurité du personnel de biodosimétrie ainsi que des victimes dans ce type d'urgence double.
Purpose: To assess the use of phosphorylated histone H2AX protein (γ-H2AX) in human blood leukocytes as a rapid screening tool for radiation biodosimetry using a method that examines the ...characteristics of γ-H2AX phosphorylation in a variety of lymphocyte subsets following exposure to radiation.
Materials and methods: Human peripheral blood exposed to 0-10 Gy of 137Cs irradiation and cultured for 0-48 h was analysed using a rapid whole blood flow cytometry assay to measure γ-H2AX phosphorylation in different lymphocyte subpopulations.
Results: Lymphocyte subsets displayed a similar linear dose response relationship, although cluster of differentiation 4+ (CD4+) and CD8+ lymphocytes were found to express H2AX phosphorylation on the order of 1.5 times higher than CD19+ lymphocytes. Phosphorylation of all lymphocyte subsets reached a maximum at 1.5 h and had essentially returned to baseline levels 24 h post-exposure.
Conclusions: Differences in the expression level of γ-H2AX between lymphocyte subsets were minimal. The usefulness of this assay for radiation biodosimetry is hampered by its relatively quick lifetime kinetics and large inter-individual variation. Therefore, it could only be useful if samples were obtained within 24 h of exposure. Even in this situation, the assay could only be used as an indicator of exposure and not a dosimeter.
A workshop entitled “Radiation-Induced Fibrosis: Mechanisms and Opportunities to Mitigate” (held in Rockville, MD, September 19, 2016) was organized by the Radiation Research Program and Radiation ...Oncology Branch of the Center for Cancer Research (CCR) of the National Cancer Institute (NCI), to identify critical research areas and directions that will advance the understanding of radiation-induced fibrosis (RIF) and accelerate the development of strategies to mitigate or treat it. Experts in radiation biology, radiation oncology and related fields met to identify and prioritize the key areas for future research and clinical translation. The consensus was that several known and newly identified targets can prevent or mitigate RIF in pre-clinical models. Further, basic and translational research and focused clinical trials are needed to identify optimal agents and strategies for therapeutic use. It was felt that optimally designed preclinical models are needed to better study biomarkers that predict for development of RIF, as well as to understand when effective therapies need to be initiated in relationship to manifestation of injury. Integrating appropriate endpoints and defining efficacy in clinical trials testing treatment of RIF were felt to be critical to demonstrating efficacy. The objective of this meeting report is to (a) highlight the significance of RIF in a global context, (b) summarize recent advances in our understanding of mechanisms of RIF, (c) discuss opportunities for pharmacological mitigation, intervention and modulation of specific molecular pathways, (d) consider the design of optimal clinical trials for mitigation and treatment and (e) outline key regulatory nonprescriptive frameworks for approval.
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