Institute for Radiation Protection and Nuclear Safety (IRSN)
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Multigenerational epigenetic and metabolomic effects of internal exposure to non-toxic doses of uranium in rats
International audienceThe increasing incidence of multifactorial diseases raises questions about the effects of the multiple environmental exposures to which the population is exposed throughout life. In this health and social context, the risk associated with low-dose exposure to uranium for the residential and occupational population, and even more so for their offspring, is still a hotly debated radiation protection issue.To study the epigenetic and phenotypic effects of chronic, non-toxic doses of uranium in somatic and male reproductive cells over several generations, recent experimental studies followed three generations of rats, the first of which was chronically exposed to uranium throughout life and even during pregnancy. Results showed that a low chronic dose of uranium resulted in increased levels of DNA methylation in the kidneys of children exposed exclusively in utero (F1) and even grandchildren concurrently exposed at the germ cell stage (F2), compared to their parents (F0). Regarding the reproductive system, rat testes also showed an altered epigenetic profile of DNA methylation and gene expression of associated enzymes over several generations. Furthermore, it is noteworthy that sperm from the last F2 generation also showed an altered DNA epigenetic fingerprint. In addition, changes in renal function were also observed in the urinary, renal and blood metabolomes of the different generations, but also in the sperm of the animals, through morphological and metabolomic changes in the spermatozoa, which could partly explain the 30% decrease in pregnancy rate measured in the second generation (F1) exposed during organogenesis and fetal development.Our preclinical studies suggest that prenatal exposure to non-toxic levels of uranium can induce epigenetic and phenotypic changes for at least two generations. They also show that these effects may be detrimental to reproductive function. However, beyond the adaptive function of epigenetic mechanisms against the metabolic effects of low-dose exposure to chemicals or ionizing radiation, these studies raise questions about the extent of heritable effects and their risk level for the development of chronic metabolic diseases in exposed adults and their offspring.L'incidence croissante des maladies multifactorielles soulève des questions sur les effets des multiples expositions environnementales auxquelles la population est soumise tout au long de la vie. Dans ce contexte sanitaire et social, le risque associé à l'exposition à de faibles doses d'uranium pour la population résidentielle et professionnelle, et plus encore pour leur progéniture, reste une question de radioprotection très débattue.Pour étudier les effets épigénétiques et phénotypiques de doses chroniques non toxiques d'uranium dans les cellules somatiques et les cellules reproductrices mâles sur plusieurs générations, des études expérimentales récentes ont suivi trois générations de rats, dont la première a été exposée de manière chronique à l'uranium tout au long de sa vie et même pendant la grossesse. Les résultats ont montré qu'une faible dose chronique d'uranium entraînait une augmentation des niveaux de méthylation de l'ADN dans les reins des enfants exposés exclusivement in utero (F1) et même des petits-enfants exposés simultanément au stade des cellules germinales (F2), par rapport à leurs parents (F0). En ce qui concerne le système reproducteur, les testicules des rats ont également montré un profil épigénétique altéré de la méthylation de l'ADN et de l'expression génique des enzymes associées sur plusieurs générations. En outre, il convient de noter que les spermatozoïdes de la dernière génération F2 présentaient également une empreinte épigénétique de l'ADN altérée. En outre, des modifications de la fonction rénale ont également été observées dans les métabolomes urinaires, rénaux et sanguins des différentes générations, mais aussi dans le sperme des animaux, par le biais de modifications morphologiques et métabolomiques des spermatozoïdes, ce qui pourrait expliquer en partie la diminution de 30 % du taux de grossesse mesuré chez la deuxième génération (F1) exposée pendant l'organogenèse et le développement du fœtus.Nos études précliniques suggèrent que l'exposition prénatale à des niveaux non toxiques d'uranium peut induire des changements épigénétiques et phénotypiques pendant au moins deux générations. Elles montrent également que ces effets peuvent être préjudiciables à la fonction de reproduction. Cependant, au-delà de la fonction adaptative des mécanismes épigénétiques contre les effets métaboliques d'une exposition à de faibles doses de produits chimiques ou de radiations ionisantes, ces études soulèvent des questions sur l'étendue des effets héréditaires et leur niveau de risque pour le développement de maladies métaboliques chroniques chez les adultes exposés et leur progéniture
Fire-induced flows for complex fire scenarios in a mechanically ventilated two-storey structure
International audienceThis work deals with smoke propagation through a multi-compartment assembly in case of a fire eventin a nuclear installation. The scientific issues are the understanding of flows involving two modes ofpropagation (vent and doorway), together with the role of mechanical ventilation and oxygen backflows tothe fire. The study is based on the analysis of two scenarios reproduced experimentally at large scale andsimulated numerically. The main outcomes concern the comparison of the flow at a doorway and at a vent,the consequence of the smoke propagation for thermal stratification and the combined effect of the fire heatrelease rate and mechanical ventilation. The results highlight the performance of CFD simulations inpredicting these complex scenarios. Low-velocity flow zones are identified, enabling the structure of theseflows and their amplitudes to be quantified. This information provides new insights to improve fire riskassessment in nuclear facilities
Development of a 14C protocol at the LMC14 for the dating of cultural heritage materials: Historial mortars. Participation in the MODIS international intercomparison campaign
International audienceABSTRACT The absolute dating of mortar by accelerator mass spectrometry (AMS) has been the subject of renewed interest for several years. International intercomparison campaigns, called MODIS (MOrtar Dating Intercomparison Study), have been carried out. The first MODIS-1 campaign highlighted limitations in mortar dating, due to the similarity between the primary material to be dated (binder) and the contaminant (exogenous CaCO 3 ). Methods have since emerged to overcome this problem and the need for a good preliminary characterization has been proven. The Laboratoire de Mesure du Carbone 14 (LMC14) took part in the second intercomparison campaign, MODIS2, by applying thermal decomposition increments to distinguish the carbonated binder, the organic matter contaminants (late in formation pyrogenic carbonate, LDH) and limestone. The LMC14 results on MODIS2 are quite conclusive on “pure” re-carbonated lime mortar binders containing little contaminant geological limestone but show their weaknesses for mortars heavily contaminated in Dolomites, which are difficult to discern from the binder. Recommendations for users of radiocarbon ( 14 C) dating on mortar-based materials are made in the conclusion
Oriented intra-granular bubble transport due to coupling of pinned bubble growth and dislocation climb
International audienceThe intra-granular fission gas release during post-irradiation annealing tests cannot be predicted if bubble motion is not taken into account. Indeed, without irradiation, the equilibrium between trapping and re-solution is completely shifted in favor of trapping, the dynamic resolution due to fission spikes no longer existing. Moreover, the sink strength of the population of intragranular bubbles is greater by a factor than the sink strength of the grain surface. Trapped in supposedly immobile bubbles, the gas would not escape from the grain, which is in contradiction with experimental observations. Several alternative scenarios involving bubble movement emerged to explain the observed fission gas release. The purpose of our work is to assess these scenarios using simulation. In a previous article, it was demonstrated that neither the movement of bubbles in a vacancy gradient, nor the Brownian movement of bubbles, nor the combination of them, could explain the large fission gas release obtained during post-irradiation annealing in our reference experiment. This demonstration was performed using a mesoscale model, called BEEP, where individual bubbles are described, along with the diffusion of vacancies from each bubble to the other, as well as from the free surface. In this paper, we extend the BEEP model to assess the role of dislocations in interaction with highly pressurized bubbles. It is concluded that a mechanism of dislocation climb coupled with the growth of highly pressurized pinned bubbles may explain the large intra-granular fission gas release in annealing conditions
Influence of short-lived radioiodines other than 131I on screening direct thyroid measurements with TCS-172 NAI(TL) survey meters
International audienceIn a nuclear emergency, one of the actions taken for the sake of public is to monitor thyroid exposure to radioiodines. Japan’s Nuclear Regulation Authority recently published a report on such monitoring and proposed direct thyroid measurements with conventional NaI(Tl) survey meters (e.g. Hitachi model TCS-172) as a primary screening method. A previous study proposed screening levels (SLs) used in these simplified measurements as the net reading values of the TCS-172 device. Age-specific SLs were derived from a thyroid equivalent dose of 100 mSv due to the inhalation intake of 131I. This study addressed the possible influence of short-lived iodine isotopes other than 131I on the simplified measurements. In preparation for such measurements, the responses of the device for 132I as an ingrowth component from 132Te, 133I, 134I and 135I in the thyroid were evaluated by numerical simulations using age-specific stylized phantoms in addition to those obtained for 131I in the previous study. The radioactivity ratios of the relevant isotopes were taken from the inventory data of the Fukushima Daiichi Nuclear Power Plant. The results were used to predict the net readings of the device when 132Te-132I and 133I as well as 131I were inhaled at 24 or 72 h after the shutdown of a nuclear power plant. In these cases, the signals from 132Te-132I and 133I become undetectable a couple of days after intake, which could lead to underestimations of the thyroid dose. To estimate the thyroid dose accurately from the simplified measurements, it is necessary to identify the exact time of intake after the shutdown and the actual physiochemical property of 132Te that affects the thyroid uptake of 132I
Directional detection of keV proton and carbon recoils with MIMAC
International audienceDirectional detection is the dedicated strategy to demonstrate that DM-like signals measured by direct detectors are indeed produced by DM particles from the galactic halo. The experimental challenge of measuring the direction of DM-induced nuclear recoils with (sub-)millimeter tracks has limited, so far, the maximal directional reach to DM masses around . In this paper, we expose the MIMAC detector to three different neutron fields and we develop a method to reconstruct the direction of the neutron-induced nuclear recoils. We measure an angular resolution better than for proton recoils down to a kinetic energy of and for carbon recoils down to a kinetic energy of . For the first time, a detector achieves the directional measurement of proton and carbon recoils with kinetic energies in the keV range without any restriction on the direction of the incoming particle. This work demonstrates that directional detection is around the corner for probing DM with masses down to
Decline of DNA damage response along with myogenic differentiation
International audienceDNA integrity is incessantly confronted to agents inducing DNA lesions. All organisms are equipped with a network of DNA damage response mechanisms that will repair DNA lesions and restore proper cellular activities. Despite DNA repair mechanisms have been revealed in replicating cells, still little is known about how DNA lesions are repaired in postmitotic cells. Muscle fibers are highly specialized postmitotic cells organized in syncytia and they are vulnerable to age-related degeneration and atrophy after radiotherapy treatment. We have studied the DNA repair capacity of muscle fiber nuclei and compared it with the one measured in proliferative myoblasts here. We focused on the DNA repair mechanisms that correct ionizing radiation (IR)-induced lesions, namely the base excision repair, the nonhomologous end joining, and the homologous recombination (HR). We found that in the most differentiated myogenic cells, myotubes, these DNA repair mechanisms present weakened kinetics of recruitment of DNA repair proteins to IR-damaged DNA. For base excision repair and HR, this decline can be linked to reduced steady-state levels of key proteins involved in these processes
Effect of natural organic matter on the speciation and transfers of Uranium(VI) in a wetland soil impacted by a former uranium mine (Roffin, France)
International audienceTo understand the fate of uranium (VI) in environments with technologically enhanced natural radioactivity, it is necessary to describe the links between its speciation and transfers in the soil-water-plant continuum. The links between speciation, lability and availability of U(VI) are major issues in forest environments where organic speciation of U(VI) predominates. The aim of the present work was to elucidate the effect of natural organic matter - and its molecular-scale fractionation on (nano)mineral surfaces during sorption- on speciation and soil-water transfers of U(VI) in a forested wetland. We carried out laboratory experiments related to a wetland soil profile showing humic and sub-surface clay horizons, with the latter being highly enriched in uranium (up to 2000 ppb) due to former U mining activities (Puy-de-Dôme, France). We used a combination of traditional batch techniques, fluorescence spectroscopy and Electrospray Ionisation mass spectrometry (ESI-MS) analyses. Results from desorption experiments provided evidence that U(VI), desorbed from wetland soil sub-samples with a solution at pH 5, is found in a colloidal fraction of 1-60 nm size. This fraction also contains iron oxide nano-minerals and condensed aromatic-type organic molecules as well as molecules with phosphate functions, while protein-like molecules are present in dissolved organic matter (DOM). This has enabled us to define experimental conditions for studying model mineral-solution systems under controlled laboratory conditions, that contain U(VI), soil OM (extracted from the wetland clayey horizon) and an iron oxide (hematite of ca. 80 nm in size). In the absence of hematite, most of U is in the form of uranyl organic colloids (> 200 nm in size), made up of an OM component of biological origin. In the ternary hematite-MO-U system, the presence of U promoted OM adsorption on hematite, -more precisely of a fraction made up of “humic-type molecules” such as condensed aromatics-. We thus observed the formation of ternary hematite surface-U-MO complexes, which were associated with a change in DOM composition. These results were consistent with those of desorption experiments, pointing to the involvement of OM and Fe-oxides in U desorption from wetland soils
Numerical assessment of the applicability of gaussian models for the prediction of near-field dispersion near urban environments
International audienceMonitoring pollutant emissions into the atmosphere is a key issue for industry and authorities. In urban environments, the presence of buildings disturbs the flow in their wake and poses specific problems of interaction between the emitted plume and the disturbed flow. Dispersion models based on a CFD approach can explicitly account for the presence of buildings and accurately represent the three-dimensional nature of the mean flow but suffer from high calculation times, often incompatible with operational time constraints. As a result, simplified, Gaussian models are still widely used to quickly provide an order of magnitude of expected consequences, especially for emergency response, despite their lack of obstacle modelling. The aim of this work is to study the applicability and scope of Gaussian models for the prediction of near-field dispersion of pollutants around industrial sites in peri-urban environments, in comparison to more complex models. To this end, the IRSN's operational Gaussian model pX and the SLAM (Safety Lagrangian Atmospheric Model) model were used to predict 85 Kr air concentration around the ORANO La Hague (France) reprocessing plant. The performance of each model was analysed through their ability to predict concentration peaks at various locations, and their sensitivity to meteorological conditions. Additionally, the sensitivity of pX to its parameterization was explored. The results show that for distances greater than one or two kilometres, the Gaussian approach can provide an acceptable prediction of field concentrations with an appropriate parameterization, while a CFD-based dispersion model tends to provide a real added value in the close vicinity of the site, where the flow and pollutant dispersion is still perturbed by the presence of buildings