Auswahl der wissenschaftlichen Literatur zum Thema „Radiosusceptibility“

Gastrointestinal (GI) microbiota maintains a symbiotic relationship with the host and plays a key role in modulating many important biological processes and functions of the host, such as metabolism, inflammation, immune and stress response. It is becoming increasingly apparent that GI microbiota is susceptible to a wide range of environmental factors and insults, for examples, geographic location of birth, diet, use of antibiotics, and exposure to radiation. Alterations in GI microbiota link to various diseases, including radiation-induced disorders. In addition, GI microbiota composition could be used as a biomarker to estimate radiosusceptibility and radiation health risk in the host. In this minireview, we summarized the documented studies on radiation-induced alterations in GI microbiota and the relationship between GI microbiota and radiosusceptibility of the host, and mainly discussed the possible mechanisms underlying GI microbiota influencing the outcome of radiation response in humans and animal models. Furthermore, we proposed that GI microbiota manipulation may be used to reduce radiation injury and improve the health of the host.

The individual response to ionizing radiation (IR) raises a number of medical, scientific, and societal issues. While the term “radiosensitivity” was used by the pioneers at the beginning of the 20st century to describe only the radiation-induced adverse tissue reactions related to cell death, a confusion emerged in the literature from the 1930s, as “radiosensitivity” was indifferently used to describe the toxic, cancerous, or aging effect of IR. In parallel, the predisposition to radiation-induced adverse tissue reactions (radiosensitivity), notably observed after radiotherapy appears to be caused by different mechanisms than those linked to predisposition to radiation-induced cancer (radiosusceptibility). This review aims to document these differences in order to better estimate the different radiation-induced risks. It reveals that there are very few syndromes associated with the loss of biological functions involved directly in DNA damage recognition and repair as their role is absolutely necessary for cell viability. By contrast, some cytoplasmic proteins whose functions are independent of genome surveillance may also act as phosphorylation substrates of the ATM protein to regulate the molecular response to IR. The role of the ATM protein may help classify the genetic syndromes associated with radiosensitivity and/or radiosusceptibility.

The evaluation of radiation-induced (RI) risks is of medical, scientific, and societal interest. However, despite considerable efforts, there is neither consensual mechanistic models nor predictive assays for describing the three major RI effects, namely radiosensitivity, radiosusceptibility, and radiodegeneration. Interestingly, the ataxia telangiectasia mutated (ATM) protein is a major stress response factor involved in the DNA repair and signaling that appears upstream most of pathways involved in the three precited RI effects. The rate of the RI ATM nucleoshuttling (RIANS) was shown to be a good predictor of radiosensitivity. In the frame of the RIANS model, irradiation triggers the monomerization of cytoplasmic ATM dimers, which allows ATM monomers to diffuse in nucleus. The nuclear ATM monomers phosphorylate the H2AX histones, which triggers the recognition of DNA double-strand breaks and their repair. The RIANS model has made it possible to define three subgroups of radiosensitivity and provided a relevant explanation for the radiosensitivity observed in syndromes caused by mutated cytoplasmic proteins. Interestingly, hyper-radiosensitivity to a low dose and adaptive response phenomena may be also explained by the RIANS model. In this review, the relevance of the RIANS model to describe several features of the individual response to radiation was discussed.

The mandate of Committee 3 of the International Commission on Radiological Protection (ICRP) is concerned with the protection of persons and unborn children when ionising radiation is used in medical diagnosis, therapy, and biomedical research. Protection in veterinary medicine has been newly added to the mandate. Committee 3 develops recommendations and guidance in these areas. The most recent documents published by ICRP that relate to radiological protection in medicine are ‘Radiological protection in cone beam computed tomography’ (ICRP Publication 129) and ‘Radiological protection in ion beam radiotherapy’ (ICRP Publication 127). A report in cooperation with ICRP Committee 2 entitled ‘Radiation dose to patients from radiopharmaceuticals: a compendium of current information related to frequently used substances’ (ICRP Publication 128) has also been published. ‘Diagnostic reference levels in medical imaging’ (ICRP Publication 135), published in 2017, provides specific advice on the setting and use of diagnostic reference levels for diagnostic and interventional radiology, digital imaging, computed tomography, nuclear medicine, paediatrics, and multi-modality procedures. ‘Occupational radiological protection in interventional procedures’ was published in March 2018 as ICRP Publication 139. A document on radiological protection in therapy with radiopharmaceuticals is likely to be published in 2018. Work is in progress on several other topics, including appropriate use of effective dose in collaboration with the other ICRP committees, guidance for occupational radiological protection in brachytherapy, justification in medical imaging, and radiation doses to patients from radiopharmaceuticals (an update to ICRP Publication 128). Committee 3 is also considering the development of guidance on radiological protection in medicine related to individual radiosusceptibility, in collaboration with ICRP Committee 1.

L’Unité de recherche UMR1296 « Radiations : Défense, Santé et Environnement » se focalise sur la réponse individuelle aux radiations ionisantes. Les travaux de l’Unité ont permis de développer un modèle mécanistique basé sur le transit cyto-nucléaire radioinduit de la protéine ATM (Radiation-Induced ATM nucleoshuttling (RIANS) model), ATM est une protéine kinase-clé de la réponse au stress génotoxique. Le modèle RIANS permet une approche prédictive robuste des réactions tissulaires qui peuvent survenir après une radiothérapie, une interprétation biologique du modèle linéaire-quadratique, formule fondamentale de la radiobiologie qui restait empirique depuis les années 70, une explication moléculaire des phénomènes radiobiologiques spécifiques des faibles doses, eux-aussi inexpliqués depuis les années 70 et une approche nouvelle de radioprotection chimique qui supplante l’anti-oxydation. Enfin, le modèle RIANS permet aujourd’hui de détecter des maladies dégénératives comme la maladie d’Alzheimer par la mise en évidence de couronnes périnucléaires d’ATM. Avec toutes ses applications, il paraissait naturel d’examiner si le modèle RIANS pouvait expliquer également les différentes étapes de la carcinogenèse et permettre de classer objectivement les maladies associées à une forte prédisposition au cancer. Cependant, pour ce faire, plusieurs tâches étaient nécessaires : mieux comprendre les mécanismes intrinsèques de la carcinogenèse présentés dans une littérature ultradocumentée et souvent confuse ; répertorier la plupart de syndromes associés à une forte prédisposition au cancer et en relever les aspects les plus spécifiques ; distinguer radiosensibilité et radiosusceptibilité au cancer et enfin définir les paramètres biologiques les plus pertinents pour mesurer indépendamment la mutabilité et la capacité de prolifération des cellules issues des syndromes majeurs associés au cancer. Cette thèse présente une variante du modèle RIANS qui permet d’intégrer et de mieux décrire les mécanismes de la carcinogenèse et un aspect quantitatif de la prédisposition au cancer, validé pour une dizaine de syndromes majeurs
The UMR1296 “Radiations: Defense, Health and Environment” Research Unit focuses on the individual response to ionizing radiation. The Unit work has made it possible to develop a mechanistic model based on the radio-induced nucleoshuttling of the ATM protein (Radiation-Induced ATM nucleoshuttling (RIANS) model), ATM is a key protein kinase in the response to genotoxic stress. The RIANS model allows a robust predictive approach to tissue reactions that can occur after radiotherapy, a biological interpretation of the linear-quadratic model, a fundamental formula of radiobiology which remained empirical since the 1970s, a molecular explanation of radiobiological phenomena specific to low doses also unexplained since the 1970s and a new approach to chemical radioprotection which replaces anti-oxidation. Finally, the RIANS model now makes it possible to detect degenerative diseases such as Alzheimer's disease by revealing perinuclear crowns of ATM. With all its applications, it seemed natural to examine whether the RIANS model could also explain the different stages of carcinogenesis and to objectively classify diseases associated with a strong predisposition to cancer. However, to reach this aim, several tasks were necessary: better understand the intrinsic mechanisms of carcinogenesis presented in an ultra-documented and often confusing literature; list most of the syndromes associated with a strong predisposition to cancer and identify their most specific aspects; distinguish radiosensitivity and radiosusceptibility to cancer and finally define the most relevant biological parameters to independently measure the mutability and proliferation capacity of cells resulting from major syndromes associated with cancer. This thesis presents a variant of the RIANS model which makes it possible to integrate and better describe the mechanisms of carcinogenesis and a quantitative aspect of predisposition to cancer, validated for around ten major syndromes

AbstractIn recent years, scientific understanding of the changes radiation makes to the various tissues of the body has vastly increased. Identification of biological markers of radiation exposure and response has become a wide field with an increasing interest across the radiation research community. This chapter introduces the concepts of individual radiosensitivity, radiosusceptibility, and radiodegeneration, which are the key factors to classify radiation responses. Biomarkers are then introduced, and their key characteristics as well as classification are explained, with a particular focus on those biomarkers which have been identified for use in epidemiological studies of radiation risk—as this is a crucial topic of current interest within radiation protection. Brief information on collection of samples is followed by a detailed presentation of predictive assays in use in different settings including clinical applications with responses assessed chiefly in tissue biopsy or blood samples. The sections toward the end of this chapter then discuss the evidence associated with the relationship between age and separately sex, and radiosensitivity, as well as some genetic syndromes associated with radiosensitivity. The final section of this chapter provides a brief summary of how our current knowledge can further support individual, personalized, uses of radiation, particularly in clinical settings.