microRNA blood signature for localized radiation injury.

A radiological accident, whether from industrial, medical, or malicious origin, may result in localized exposure to high doses of ionizing radiations, leading to the development of local radiation injury (LRI), that may evolve toward deep ulceration and necrosis of the skin and underlying tissues. Early diagnosis is therefore crucial to facilitate identification and management of LRI victims. Circulating microRNAs (miRNA) have been studied as potential diagnostic biomarkers of several diseases including hematological defects following whole-body irradiation (WBI). This study aims to identify a blood miRNA signature associated with LRI in a preclinical C57BL/6J mouse model of hindlimb irradiation using different 10-MV X-ray doses that lead to injuries of different severities. To this end, we first performed broad-spectrum plasma miRNA profiling, followed by a targeted validation step, on two independent animal cohorts. Using a multivariate sparse partial least square discriminant analysis, we identified a panel of eight circulating miRNAs able to segregate mice according to LRI severity. Interestingly, these miRNAs were previously associated with WBI (miR-150-5p, miR-342-3p, miR-146a-5p), inflammation (miR-18a-5p, miR-148b-3p, miR-532-5p) and skin diseases (miR-139-5p, miR-195-5p). Our results suggest the use of circulating miRNAs as suitable molecular biomarkers for LRI prognosis and diagnosis.

Variation of 4 MV X-ray dose rate in fractionated irradiation strongly impacts biological endothelial cell response in vitro.

PURPOSE: Even though X-ray beams are widely used in medical diagnosis or radiotherapy, the comparisons of their dose rates are scarce. We have recently demonstrated in vitro (clonogenic assay, cell viability, cell cycle, senescence) and in vivo (weight follow-up of animals and bordering epithelium staining of lesion), that for a single dose of irradiation, the relative biological effectiveness (RBE) deviates from 1 (up to twofold greater severe damage at the highest dose rate depending on the assay) when increasing the dose rate of high energy X-ray beams. MATERIAL AND METHODS: To further investigate the impact of the dose rate on RBE, in this study, we performed in vitro fractionated irradiations by using the same two dose rates (0.63 and 2.5 Gy.min-1) of high-energy X-rays (both at 4 MV) on normal endothelial cells (HUVECs). We investigated the viability/mortality, characterized radiation-induced senescence by using flow cytometry and measured gene analysis deregulations on custom arrays. RESULTS: The overall results enlighten that, in fractionated irradiations when varying the dose rate of high-energy X-rays, the RBE of photons deviates from 1 (up to 2.86 for viability/mortality experiments performed 21 days postirradiation). CONCLUSION: These results strengthen the interest of multiparametric analysis approaches in providing an accurate evaluation of the outcomes of irradiated cells in support of clonogenic assays, especially when such assays are not feasible.

The stromal vascular fraction mitigates radiation-induced gastrointestinal syndrome in mice.

BACKGROUND: The intestine is particularly sensitive to moderate-high radiation dose and the development of gastrointestinal syndrome (GIS) leads to the rapid loss of intestinal mucosal integrity, resulting in bacterial infiltration, sepsis that comprise patient survival. There is an urgent need for effective and rapid therapeutic countermeasures. The stromal vascular fraction (SVF) derived from adipose tissue is an easily accessible source of cells with angiogenic, anti-inflammatory and regenerative properties. We studied the therapeutic impact of SVF and its action on the intestinal stem cell compartment. METHODS: Mice exposed to the abdominal radiation (18 Gy) received a single intravenous injection of stromal vascular fraction (SVF) (2.5 × 106 cells), obtained by enzymatic digestion of inguinal fat tissue, on the day of irradiation. Mortality was evaluated as well as intestinal regeneration by histological analyses and absorption function. RESULTS: The SVF treatment limited the weight loss of the mice and inhibited the intestinal permeability and mortality after abdominal irradiation. Histological analyses showed that SVF treatment stimulated the regeneration of the epithelium by promoting numerous enlarged hyperproliferative zones. SVF restored CD24+/lysozyme- and Paneth cell populations in the ISC compartment with the presence of Paneth Ki67+ cells. SVF has an anti-inflammatory effect by repressing pro-inflammatory cytokines, increasing M2 macrophages in the ileum and anti-inflammatory monocyte subtypes CD11b+Ly6clowCX3CR1high in the spleen. CONCLUSIONS: Through the pleiotropic effects that contribute to limiting radiation-induced lethality, SVF opens up attractive prospects for the treatment of emergency GIS.

IRPA GUIDANCE-THE ROLE OF STAKEHOLDERS, RADIATION PROTECTION CULTURE AND ETHICS IN EMERGENCY PREPAREDNESS.

The International Radiation Protection Association, IRPA, promotes the excellence in radiation protection by providing benchmarks of good practice, as well as enhancing professional competence and networking. In relation to emergency situations, including post-accident and recovery phases, a key issue is the ability of the system of protection to take a broader view of societal values, along with the need to develop processes which support and respect the dignity and well-being of the affected populations. Regarding the various situations of radiation exposure, IRPA's activities include aspects which can contribute to medical preparedness in radiation emergencies, focusing particularly on stakeholder engagement, radiation protection culture, the ethical dimensions of radiation protection and public understanding of risks. As it is a combination of science, experience, ethical and social values, radiation protection culture promotes radiation risk awareness in the different exposure situations, including the implementation of countermeasures in radiation and nuclear emergencies and post-accident situations, with attention also on medical countermeasures.

[Iodine distribution around nuclear power plants]. / Distribution d'iode autour des centrales nucléaires.

Iodine distribution around nuclear power plants. In the event of a radioactive release during a nuclear accident, public protection strategy is based on three key measures: 1) taking shelter, 2) administration of stable iodine and 3) evacuation depending on conditions. Since the Chernobyl nuclear accident, stable iodine has been administered to prevent thyroid cancer in children. In 1997, the government decided to arrange for the pre-distribution of iodine tablets to members of the public residing in off-site emergency planning areas, within a 10-km radius of a nuclear power plant. This radius will shortly be extended to 20 km and a stock of iodine tablets will also be supplied to each French département. This article refers back to the 2016 distribution campaign, which was an opportunity for informing citizens about the full range of protective measures to be taken in the event of a radioactive release in order to foster a real risk-prevention culture.

Distribution d'iode autour des centrales nucléaires. En cas de rejet radioactif lors d'un accident nucléaire, la stratégie de protection des populations repose sur trois mesures principales : la mise à l'abri, la prise d'iode stable et l'évacuation en fonction de la situation. L'ingestion d'iode stable prévient le risque de cancer de la thyroïde observé chez les enfants après l'accident nucléaire de Tchernobyl. Dès 1997, le gouvernement a pris la décision d'organiser une pré-distribution des comprimés d'iode pour les populations résidant dans les zones du Plan Particulier d'Intervention, soit dans un rayon de 10 km autour des centrales nucléaires, rayon qui sera étendu prochainement à 20 km et par la mise à disposition de stocks d'iode dans chaque département français. Cet article revient sur la campagne de distribution de 2016 qui a été une opportunité pour sensibiliser les citoyens à l'ensemble des actions de protection en cas de rejets radioactifs afin de développer une véritable culture du risque.

[Nuclear-power-plant accidents: thyroid cancer incidence and radiation-related health effects from the Chernobyl accident]. / Accident de centrale nucléaire et risque de cancer de la thyroïde : les conséquences sanitaires de Tchernobyl.

Following the Chernobyl accident, enormous amounts of radioisotopes were released in the atmosphere and have contaminated surrounding populations in the absence of rapid protective countermeasures. The highest radiation doses were delivered to the thyroid gland, and the only direct consequence of radiation exposure observed among contaminated population is the increased incidence of thyroid cancers among subjects who were children in 1986 and who lived at that time in Belarus, Ukraine or Russia.