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International audience; Existing and future nuclear fusion technologies involve the production and use of large quantities of tritium, a highly volatile, but low toxicity beta-emitting isotope of hydrogen. Tritium has received international attention because of public and scientific concerns over its release to the environment and the potential health impact of its internalization. This article provides a brief summary of the current state of knowledge of both the biological and regulatory aspects of tritium exposure; it also explores the gaps in this knowledge and provides recommendations on the best ways forward for improving our understanding of the health effects of low-level exposure to it. Linking health effects specifically to tritium exposure is challenging in epidemiological studies due to high uncertainty in tritium dosimetry and often suboptimal cohort sizes. We therefore argued that limits for tritium in drinking water should be based on evidence derived from controlled in vivo animal tritium toxicity studies that use realistically low levels of tritium. This article presents one such mouse study, undertaken within an international collaboration, and discusses the implications of its main findings, such as the similarity of the biokinetics of tritiated water (HTO) and organically bound tritium (OBT) and the higher biological effectiveness of OBT. This discussion is consistent with the position expressed in this article that in vivo animal tritium toxicity studies carried out within large, multi-partner collaborations allow evaluation of a great variety of health-related endpoints and essential to the development of international consensus on the regulation of tritium levels in the environment. Environ. Mol. Mutagen. 59586–594, 2018. © 2018 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. © 2018 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society

International audience; The aim of this study was to carry out a comprehensive examination of potential genotoxic effects of low doses of tritium delivered chronically to mice and to compare these effects to the ones resulting from equivalent doses of gamma-irradiation. Mice were chronically exposed for one or eight months to either tritiated water (HTO) or organically bound tritium (OBT) in drinking water at concentrations of 10 kBq/L, 1 MBq/L or 20 MBq/L. Dose rates of internal β-particle resulting from such tritium treatments were calculated and matching external gamma-exposures were carried out. We measured cytogenetic damage in bone marrow and in peripheral blood lymphocytes (PBLs) and the cumulative tritium doses (0.009 - 181 mGy) were used to evaluate the dose-response of OBT in PBLs, as well as its relative biological effectiveness (RBE). Neither tritium, nor gamma exposures produced genotoxic effects in bone marrow. However, significant increases in chromosome damage rates in PBLs were found as a result of chronic OBT exposures at 1 and 20 M Bq/L, but not at 10 kBq/L. When compared to an external acute gamma-exposure ex vivo, the RBE of OBT for chromosome aberrations induction was evaluated to be significantly higher than 1 at cumulative tritium doses below 10 mGy. Although found non-existent at 10 kBq/L (the WHO limit), the genotoxic potential of low doses of tritium ( > 10 kBq/L), mainly OBT, may be higher than currently assumed. © Roch-Lefèvre et al.

Following large-scale accidental overexposure to ionising radiation, a rapid triage of the exposed population can be performed by scoring dicentrics and ring chromosomes in 50 metaphases. This is rapid but not accurate. Following this triage step, the dose can be estimated by scoring 500 metaphases. This is lengthy but very accurate. To improve the methodology, we propose using software for automatic dicentric scoring, which was tested on 63 victims of a radiological accident. The method using automatic dicentric scoring was compared with the standard methods of manual scoring. The comparison of the doses obtained shows that the automatic method could replace the two steps of the manual scoring (50 and 500 metaphases). In fact, the automatic scoring method is more accurate than the manual scoring of 50 metaphases and can therefore be used for triage. © EDP Sciences, 2010.; En cas d’accident radiologique impactant un grand nombre d’individus, il est primordial de différencier rapidement les individus exposés des individus non exposés. Le laboratoire de dosimétrie biologique de l’IRSN développe des méthodes pour répondre à ce type de situation. La méthode de référence est basée sur une estimation rapide de la dose après comptage des dicentriques et des anneaux dans 50 métaphases. À l’issue de cette étape de tri de la population exposée, une estimation plus précise de la dose reçue peut être nécessaire. Cette étape est longue car elle nécessite l’observation des aberrations chromosomiques dans au moins 500 métaphases. Pour améliorer cette méthodologie en deux étapes, nous avons étudié l’utilisation d’un logiciel de détection automatique des dicentriques dans un cas réel d’accident radiologique impliquant 63 victimes. Cette méthode a été comparée aux méthodes manuelles de références. La comparaison des doses obtenues montre que la méthode automatique peut remplacer les deux étapes du comptage manuel (50 et 500 métaphases), car elle cumule les avantages de chacune d’elles : rapidité et précision.

In the first part of this review, we examined through an extensive literature review, the influence of various factors related to the individual (age, sex, alcohol and tobacco) on the rate of translocation. In the second part, our literature review focused on the study of more toxic factors related to occupational exposure. All toxic agents tested induced an increase in the translocation rate in lymphocytes of exposed people. However 2 agents (polycyclic aromatic hydrocarbons -PAHs- and heavy metals) increase significantly the rate of translocation of exposed persons. This increase is function to the dose and duration of exposure. The sensitivity of FISH technique has highlighted the necessity of protective equipment. For all the toxic factors related to occupational exposure, protective equipment or exposure conditions reduced significantly the translocations rate of exposed subjects. Thus the FISH technique could be an exposure warning indicator. In conclusion, it is important to know as well the personnel and occupational curriculum of an individual if a retrospective dose assessment is required. Thus, the rate of translocations threshold will be based on the lifestyle rate. © EDP Sciences, 2010.; Dans la première partie de cette revue, nous avons examiné, au travers d’une étude bibliographique approfondie, l’influence de différents facteurs liés à l’individu (âge, sexe, consommation d’alcool ou de tabac) sur le taux de translocations. Dans cette seconde partie, notre revue de la littérature s’est attachée à l’étude de facteurs plus toxiques liés à une exposition professionnelle. Tous les agents toxiques analysés induisent une augmentation du taux de translocations au sein des lymphocytes des personnes exposées. Cependant 2 agents (hydrocarbures aromatiques polycycliques –HAPs- et les métaux lourds) augmentent de manière significative le taux des translocations des personnes exposées. Ce type d’agents toxiques augmente le taux de translocations proportionnellement à la dose et à la durée d’exposition. La sensibilité de la technique FISH a permis de mettre en évidence la nécessité et le bon fonctionnement des équipements de protection. Pour tous les facteurs toxiques liés à une exposition professionnelle, un équipement de protection adapté et ergonomique ou bien la période d’exposition ont réduit significativement le taux de translocations des individus exposés. Ainsi la technique FISH pourrait servir d’indicateur d’exposition. En conclusion, afin d’évaluer rétrospectivement l’exposition d’un individu, il est important de connaitre le plus précisément possible son curriculum clastogène et son âge. Ainsi, un taux de translocations limite pourrait être établi en fonction de l’impact des expositions professionnelles et environnementales connues aujourd’hui et de la connaissance du passé de l’individu.

The assessment of exposure to ionizing radiation, carried out long time after exposure, is currently performed by scoring of translocations, a specific type of chromosomal aberrations. The translocations rate observed in peripheral blood lymphocytes of exposed subjects is compared to that observed in a control population. However, the translocation specificity towards radiation exposure is not clearly identified. To avoid any hasty conclusion, it is necessary to identify all the factors likely to induce translocation. To our knowledge, no study has thus far examined the effects of all these different factors on translocation rates. A review of the literature thus allowed us to assess the impact of host factors and lifestyle on the production of translocations. This study confirms that age appears to be the factor having the greatest impact on the rate of translocations, especially over 60 years. To date, the factor "age" is already considered in estimating the impact of radiation on the rate of translocation for all age groups. However, the study also shows that this rate varies significantly when the patient is exposed simultaneously and significantly towards many lifestyle agents. A precise threshold translocation rate should thus be established as a function of known behavioral exposures, below which it is impossible to conclude that radiological exposure has occurred. The effects of chemicals on the translocation rate after occupational exposure will be the subject of a second part. © EDP Sciences, 2010.; L’évaluation de l’exposition aux rayonnements ionisants, effectuée longtemps après l’exposition, est actuellement réalisée en dénombrant les aberrations chromosomiques de type translocations. Le taux de ces translocations observées dans les lymphocytes des personnes exposées est comparé au taux observé au sein d’une population contrôle. Toutefois, la spécificité des translocations vis-à-vis de l’irradiation n’est pas clairement identifiée. Afin d’éviter toute conclusion hâtive, il est nécessaire d’identifier tous les facteurs susceptibles d’induire des translocations. À notre connaissance, aucune synthèse sur l’effet de ces différents facteurs sur le taux de translocations n’a été réalisée à ce jour. Cette recherche bibliographique a confirmé l’impact de certains facteurs personnels sur l’augmentation des translocations. Cette étude corrobore que l’âge s’avère être le facteur ayant le plus d’impact sur le taux de translocations, notamment après 60 ans. À ce jour, le facteur « âge » est déjà considéré dans l’estimation du taux de translocations après suspicion d’exposition aux rayonnements ionisants pour toutes les classes d’âge. L’étude montre également que ce taux varie significativement lorsque le patient est exposé simultanément et de manière importante et chronique à une combinaison alcool et tabac. Ainsi, une courbe du taux de translocations devrait être établie en fonction de la consommation excessive de ce type d’agent pour chaque individu. Ainsi il serait alors possible de déterminer le taux de translocations induit uniquement par une exposition radiologique. Les effets des agents toxiques sur le taux de translocations après exposition professionnelle feront l’objet d’une deuxième partie.

To test a CellProfiler pipeline for automated counting and characterization of gamma-H2AX foci in color images of human cultured cells.A431 cells were irradiated and stained for gamma-H2AX foci detection. Sets of color images were analyzed visually, and findings were compared with those using FociCounter and CellProfiler software.The CellProfiler pipeline includes some proprieties not present in FociCounter, such as the automatic detection of nuclei, the detection of touching nuclei and the rejection of nuclei that touch the border of the image. The time required for manual operation is associated with the number of images analyzed visually or by FociCounter but not for the CellProfiler program. CellProfiler reduced manual operation time and is about 4 times faster than semiautomatic detection using FociCounter and 10 times faster than visual counting.We conclude that CellProfiler and FociCounter are reliable tools for measuring gamma-H2AX foci. However, CellProfiler overcomes the limitations of the FociCounter program and is able to detect nuclei automatically, saving considerable manual operation.