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Notre projet porte sur les facteurs d'expositions professionnelles en lien avec les activités nucléaires. Dans ce contexte, les travailleurs peuvent être exposés à des polluants chimiques, en particulier sous forme d'aérosols particulaires, mais également des stresseurs radiologiques. Ainsi, des rats adultes ont été exposés à l'inhalation d'un aérosol polydispersé de particules de tungstène et/ou une irradiation gamma à faible dose. Notre objectif est de déterminer si des effets différentiels sont observés selon les schémas d'exposition sur des processus cibles impliqués dans la toxicité cérébrale. Ces processus comprennent, en particulier, l'intégrité neuronale et la neuroinflammation, analysées 24 heures et 28 jours après exposition dans le cortex frontal et le bulbe olfactif. Les résultats révèlent des différences significatives entre les groupes coexposés et contrôles pour plusieurs paramètres (densité cellulaire corticale et densité microgliale), mais pas entre les groupes exposés à un seul stresseur et les groupes contrôles. Ces résultats suggèrent une synergie entre nos deux stresseurs, hypothèse qui va faire l'objet d'études complémentaires. De plus, nous observons une pérennité de ces effets à 28 jours, ce qui implique de potentiels effets sur le long terme., Our project focuses on occupational exposures linked to nuclear facilities. In this context, workers may be exposed to chemical pollutants, especially in the form of particulate aerosols, but also to radiological stressors. Thus, male adult rats were exposed to the inhalation of a polydisperse tungsten particle aerosol and/or a low dose gamma irradiation. Our goal is to determine if differential effects can be observed on target processes involved in cerebral toxicity depending on our exposure protocols. These processes include, in particular, neuronal integrity and neuroinflammation, analyzed at 24 hours and 28 days after exposure in the frontal cortex and olfactory bulb. Our results reveal significant differences between co-exposed and control groups for several parameters (cortical cellular density and microglial density), but not between single stressor and control groups. These results suggest a synergy between our two stressors. This hypothesis will be furthered studied. In addition, we also observe a persistence of our effects after 28 days, which could imply long-term effects.

Current understanding of mechanisms of cellular resistance to genotoxic stress is incomplete but is critical for a variety of medical applications. Recent developments in the CRISPR/Cas technologies open new opportunities for targeted interrogation of resistance genes and pathways. In the present work, we used nuclease dead Cas9 constructs to achieve targeted overexpression of endogenous genes encoding two essential subunits of DNA damage sensor complex, XPC and HR23B, in HEK293T cells. Both individual and simultaneous overexpression of the two genes was achieved and the effects on cellular resistance to ionizing radiation and paraquat was examined. Using the fluorometric microculture cytotoxicity assay, we showed that simultaneous, but not separate overexpression of the two genes lead to a 30% increase in survivability. Irradiated cells that overexpressed both XPC and HR23B genes showed higher clonogenic capacity and proliferation rate compared to the irradiated transfection control as revealed by the clonogenic survival assay. Modulation of the gene expression did not affect cell resistance to paraquat. In summary, our results demonstrate a high potential of CRISPR/dCas9-enabled multiplex overexpression of stress-response genes in functionally justified combinations, exemplified here by the XPC-HR23B complex, for achieving an enhanced cellular radioresistance.

Until 1981 the personnel of the Soviet Antarctic Expeditions traveled between the USSR and Antarctica by sea. In that year movements of personnel by air began. The critical factor was that in 1980 the first Soviet snow airstrip for heavy wheeled aircraft was built at Molodezhnaya. The authors review the development of the techniques required for constructing such an airstrip on snow and firn.