Tritiated Steel Micro-Particles: Computational Dosimetry and Prediction of Radiation-Induced DNA Damage for In Vitro Cell Culture Exposures.

Biological effects of radioactive particles can be experimentally investigated in vitro as a function of particle concentration, specific activity and exposure time. However, a careful dosimetric analysis is needed to elucidate the role of radiation emitted by radioactive products in inducing cyto- and geno-toxicity: the quantification of radiation dose is essential to eventually inform dose-risk correlations. This is even more fundamental when radioactive particles are short-range emitters and when they have a chemical speciation that might further concur to the heterogeneity of energy deposition at the cellular and sub-cellular level. To this aim, we need to use computational models. In this work, we made use of a Monte Carlo radiation transport code to perform a computational dosimetric reconstruction for in vitro exposure of cells to tritiated steel particles of micrometric size. Particles of this kind have been identified as worth of attention in nuclear power industry and research: tritium easily permeates in steel elements of nuclear reactor machinery, and mechanical operations on these elements (e.g., sawing) during decommissioning of old facilities can result in particle dispersion, leading to human exposure via inhalation. Considering the software replica of a representative in vitro setup to study the effect of such particles, we therefore modelled the radiation field due to the presence of particles in proximity of cells. We developed a computational approach to reconstruct the dose range to individual cell nuclei in contact with a particle, as well as the fraction of "hit" cells and the average dose for the whole cell population, as a function of particle concentration in the culture medium. The dosimetric analysis also provided the basis to make predictions on tritium-induced DNA damage: we estimated the dose-dependent expected yield of DNA double strand breaks due to tritiated steel particle radiation, as an indicator of their expected biological effectiveness

A 3D In Vitro Model of the Human Airway Epithelium Exposed to Tritiated Water: Dosimetric Estimate and Cytotoxic Effects

International audienceTritium has been receiving worldwide attention, particularly because of its production and use in existing fission reactors and future nuclear fusion technologies, leading to an increased risk of release in the environment. Linking human health effects to low-dose tritium exposures presents a challenge for many reasons. Among these: biological effects strongly depend on the speciation of tritiated products and exposure pathway; large dosimetric uncertainties may exist; measurements using in vitro cell cultures generally lack a description of effects at the tissue level, while large-scale animal studies might be ethically questionable and too highly demanding in terms of resources. In this context, threedimensional models of the human airway epithelium are a powerful tool to investigate potential toxicity induced upon inhalation of radioactive products in controlled physiological conditions. In this study we exposed such a model to tritiated water (HTO) for 24 h, with a range of activity levels (up to ;33 kBq ll–1 cm–2). After the exposures, we measured cell viability, integrity of epithelial layer and pro-inflammatoryresponse at different post-exposure time-points. We also quantified tritium absorption and performed dosimetric estimates considering HTO passage through the epithelial layer, leading to reconstructed upper limits for the dose to the tissue of less than 50 cGy cumulative dose for the highest activity. Upon exposure to the highest activity, cell viability was not decreased; however, we observed a small effect on epithelial integrity and an inflammatory response persisting after seven days. These results represent a reference condition and will guide future experiments using human airway epithelium to investigate the effects of other peculiar tritiated products

Atelier « Science and values in radiological protection »

L’AEN (Agence pour l’énergie nucléaire) a organisé un atelier « Sciences and values in radiological protection » afin d’identifier les voies possibles d’intégration en radioprotection de certains résultats du domaine de la recherche sur les effets biologiques et sur la santé des rayonnements ionisants. Trois thèmes d’actualité ont été développés : les effets non ciblés, la radiosensibilité individuelle et les maladies cardio-vasculaires. À l’issue de ces journées, des recommandations ont été émises envers les scientifiques, les radioprotectionnistes et les parties prenantes

Radiation-induced neurovascular injury

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Criticality accident dosimetry at CEA facilities use of snac2 type neutron zone spectrometer

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Suspicion of radiological overexposures in Georgia (1998): The role of IPSN

At the end of July 1998, three 137Cs sources (between 0.17 and 150 GBq) were found in the vicinity of the village of Matkhoji, located at 300 km to the west of Tbilissi. This site was a former Russian military base, abandoned since 1992 and used now as pasture and a playground for the children. The Georgian Environment Ministry requested assistance from IAEA which sent a mission to the site. This established that a predominantly chronic exposure of part of the population of the village has occurred. The IAEA requested technical assistance from IPSN. A mission, made up of 4 people from IPSN and a representative of the IAEA went to the site from 12 to 17 October 1998. This mission collected information on the circumstances of the exposure and selected a potentially explored cohort of 112 people, in three groups: children of more than five years and adults of less than 50 years attending the site and members of a family who had a source in their cattle shed. An analysis of hematologic parameters was performed on these people and 85 blood samples were taken for biological dosimetry. The hematologic analysis carried out on the spot did not show any particular anomaly. The biological dosimetry by scoring of unstable chromosome aberrations (dicentric, rings centric, fragments) in blood peripheral lymphocytes was performed on blood samples after air transportation to the specialised laboratory (LDBM) of the IPSN Two successive procedures were initiated. The first was a quick phase of triage not very precise but intended to check if some of these people presented obvious signs of irradiation. Only 50 cells per subject were scored. Seven days were needed to complete this phase. Dicentrics were found in three people only indicating a whole-body dose not exceeding 0.5 Gy on average. This triage was followed of a more complete but longer examination, where chromosome aberrations were scored in 250 cells. Six weeks were necessary to score 22 000 cells from the 85 people. In total, 30 dicentrics were scored among only 17 Georgian patients. The highest dose to the whole body estimated from a reference calibration curve was 0.3 Gy The majority of these dicentrics was found in the children having played on several occasions in the former military camp. Unfortunately, the information provided by the population was too fragmentary to permit an effective reconstruction of the individual doses

Characterization of the acute inflammatory response after irradiation in mice and its regulation by interleukin 4 (Il4).

International audienceThe aim of this study was to determine the effects of total-body irradiation of mice on the acute release of a panel of several mediators of inflammation and to evaluate the efficacy of Il4 in regulating these radiation-induced modifications. We studied the effects of exposure of C57BL6/J mice to 8 Gy gamma rays on the early release of cytokines, chemokines, acute-phase proteins, prostaglandins and corticosterone in either plasma or tissues compared to those observed after intraperitoneal injection of lipopolysaccharide from 1 h to 3 days after stimulation. During the characterization of the acute inflammatory response induced by radiation or lipopolysaccharide, we observed differences both in the type of mediators produced and in the time course of release. We next determined the anti-inflammatory potential of Il4 in this model of total-body irradiation. We found that Il4 was able to down-regulate the radiation-induced production of mediators of inflammation such as Gro1 (also known as KC, N51) in plasma and lung, corticosterone in blood, Il1b in lung, and prostaglandin E(2) in colon, suggesting the anti-inflammatory potential of Il4 in regulating the radiation-induced response

The assessment and management of risks associated with exposures to short-range Auger- and beta-emitting radionuclides. State of the art and proposals for lines of research

International audienceThe assessment and management of risks associated with exposures to ionising radiation are defined by the general radiological protection system, proposed by the International Commission on Radiological Protection (ICRP). This system is regarded by a large majority of users as a robust system although there are a number of dissenting voices, claiming that it is not suitable for estimating the risks resulting from internal exposures. One of the specific issues of internal exposure involves short-range radiations such as Auger and beta particles. Auger- and beta-emitting radionuclides can be distributed preferentially in certain tissue structures and even in certain cellular organelles, according to their chemical nature and the vector with which they are associated. Given the limited range of the low-energy electrons in biological matter, this heterogeneous distribution can generate highly localised energy depositions and exacerbate radiotoxic responses at cellular level. These particularities in energy distribution and cellular responses are not taken into account by the conventional methods for the assessment of risk. Alternative systems have been proposed, based on dosimetry conducted at the cellular or even molecular level, whose purpose is to determine the energy deposition occurring within the DNA molecule. However, calculation of absorbed doses at the molecular level is not sufficient to ensure a better assessment of the risks incurred. Favouring such a microdosimetric approach for the risk assessments would require a comprehensive knowledge of the biological targets of radiation, the dose-response relationships at the various levels of organisation, and the mechanisms leading from cellular energy deposition to the appearance of a health detriment. The required knowledge is not fully available today and it is not yet possible to link an intracellular energy deposition to a probability of occurrence of health effects or to use methods based on cellular dosimetry directly. The imperfections of the alternative approaches proposed so far should not discourage efforts. Protection against exposure to Auger and low-energy beta emitters would benefit from mechanistic studies, dedicated to the study of energy depositions of the radionuclides in various cellular structures, but also from radiotoxicological studies to define the relative biological effectiveness of the various Auger emitters used in medicine and of certain low-energy beta emitters, whose behaviour may depend greatly on their chemical form during intake. The scientific expertise, as well as the human and physical resources needed to conduct these studies, is available. They could be now mobilised into international low-dose research programmes, in order to ultimately improve the protection of people exposed to these specific radionuclides. © 2013 IOP Publishing Ltd

Application thérapeutique de l'IL-4 dans un modèle de souris irradiées corps entier à dose létale

International audienceIn the present study, we determined the consequences of IL-4 treatment on survival, hematopoietic recovery as well as acute inflammatory response of irradiated mice. Mice were total body irradiated with lethal doses of γ-rays and treated with IL-4 30 min or 2 h after exposure. Our data show an enhancement of the 30-day survival after 8 Gy irradiation, from 20% for placebo-treated mice to 75% with IL-4. It is generally admitted that the death of animals occurring in this dose range is due to hematopoietic syndrome. Therefore, we determined the efficacy of IL-4 on promoting the recovery of blood cell counts and progenitors in bone marrow. The hematopoietic status of animals is the same whether or not treated with IL-4. Given the anti-inflammatory properties of IL-4, we studied the consequences of IL-4 treatment on the inflammatory response within 24 h after 8 Gy exposure. We have shown that IL-4 treatment led to a limitation of the release of inflammatory mediators, such as IL-1β or KC, in the plasma or tissues of irradiated mice. On the other hand, IL-4 improved the radio-induced metabolic and functional damages in the central nervous system. In conclusion, our results have shown an enhanced survival of IL-4 treated irradiated mice without improvement of hematopoietic reconstitution. Therapeutic potential of IL-4 could result, at least in part, from the limitation of the radio-induced inflammatory response. © 2002 EDP Sciences