Health Effects of Naturally Radioactive Water Ingestion: The Need for Enhanced Studies

Background: Radiological pollution is a potentially important aspect of water quality. However, relatively few studies have been conducted to document its possible health effects

L'intervention du facteur « temps » dans l'interprétation du test de Rorschach

Dublineau J., Soboul I. L'intervention du facteur « temps » dans l'interprétation du test de Rorschach. In: Bulletin du groupement français du Rorschach, n°7, 1955. pp. 27-34

Uranium appauvri: Perturbateur métabolique?

The presence of uranium in the environment can lead to long-term contamination of the food chain and of water intended for human consumption and thus raises many questions about the scientific and societal consequences of this exposure on population health. Although the biological effects of chronic low-level exposure are poorly understood, results of various recent studies show that contamination by depleted uranium (DU) induces subtle but significant biological effects at the molecular level in organs including the brain, liver, kidneys and testicles. For the first time, it has been demonstrated that DU induces effects on several metabolic pathways, including those metabolising vitamin D, cholesterol, steroid hormones, acetylcholine and xenobiotics. This evidence strongly suggests that DU might well interfere with many metabolic pathways. It might thus contribute, together with other man-made substances in the environment, to increased health risks in some regions.Année de parution : 2011 La présence d’uranium dans l’environnement peut conduire à long terme à une contamination de la chaîne alimentaire et/ou des eaux destinées à la consommation humaine, soulevant alors de nombreuses interrogations scientifiques et sociétales quant aux conséquences de cette exposition sur la santé des populations. Les effets biologiques d’une exposition chronique à de faibles niveaux sont peu connus. Cependant, les résultats de différentes études récentes montrent que ce type de contamination à l’uranium appauvri induirait des effets biologiques de types moléculaires subtils, mais significatifs, dans des organes tels que le cerveau, le foie, les reins et les testicules. La grande nouveauté dans les effets induits après contamination interne par l’uranium est la mise en évidence d’effets sur un certain nombre de métabolismes majeurs de l’organisme comme le métabolisme de la vitamine D, du cholestérol, des hormones stéroïdiennes, de l’acétylcholine et des xénobiotiques. Ces données scientifiques suggèrent fortement que l’uranium est susceptible d’interférer avec de nombreuses voies métaboliques. Ainsi, il pourrait contribuer, avec d’autres substances artificielles présentes dans l’environnement, à l’augmentation des risques sanitaires dans certaines régions du globe

ATP-Sensitive Potassium Channels: a Potential Target of Chronic Contamination with Cesium 137.

Radioactive fallout of the Chernobyl accident led to 137cesium (137Cs) dispersion in the environment. This radionuclide has a half-life of 30 years and is therefore still present as a contaminant in the food chain. Thus, populations living in radioactive-polluted regions are chronically exposed and many questions are raised about public health, notably about cardiovascular pathologies. 137Cs is known as an ionic analogue of potassium. Potassium ions are transported via membranous ATP-sensitive potassium (KATP) channels among others. They are made of a combination of two types of subunits: the pore-forming subunits Kir6.x (Kir6.1 or Kir6.2) and regulatory subunits sulfonylurea receptor SUR (SUR1 or SUR2). These subunits are differently expressed according to the tissue and its excitable or non-excitable status. KATP channels are present in many organs and have leading roles in cardiac and muscle functionalities and also in homeostasis, hormone secretion, immunity response or cellular proliferation. Therefore, we carried out in vivo experimental studies in rats with 137Cs chronic exposure to study biological effects on this channel type. Gene expressions of Kir6.1, Kir6.2, SUR1 and SUR2 subunits in heart, skeletal muscle, hypothalamus and kidney were analyzed in adult rats exposed to 137Cs through drinking water for several months (1,3 or 9 months) at a dose of 6500Bq/l (610Bq/kg/day). We noticed gene expression modifications in the heart between the control and the contaminated group, with an increase in Kir6.1 and SUR1 (+194% and +164% respectively, p<0.05) for 1 month-contaminated rats and an increase in SUR2 (+132%, p<0.01) for 3 month-contaminated rats. At the opposite, there were a decrease in Kir6.2 and SUR1 (­57% and ­44% respectively, p<0.001) for 9 month-contaminated rats. However these modifications were not bound to any protein expression disturbances in the heart for rats exposed to 137Cs for 3 and 9 months. In conclusion, a heart transcriptional regulation of KATP channels is affected by a chronic contamination at a post-accidental 137Cs dose, which suggests a specific sensitivity of heart as compared to other organs. Moreover, the short-term increase induced at 1 and 3 months was followed by a decrease at 9 months: these time-dependant variations could evoke a tissue regulation during chronic 137Cs contamination. However this chronic exposure doesnt seem to breed any pathological disorders in rats as indicated by complementary histological and ECG data (Gueguen et al., 2008). It would be therefore interesting to expand our analyses to juvenile animals supposed to be more sensitive to radionuclide exposure

Discrimination of Radiotoxic and Chemotoxic Effects of Uranium on Mouse Embryo Fibroblasts

Uranium (U) is a natural radioactive heavy metal used in the nuclear industry, in different forms with different isotopic compositions (natural, depleted or enriched in 235U) and solubilities. Uranium internal exposure is a major risk for the nuclear workers. Uranium uptake can occur accidentally after inhalation, ingestion, or absorption through intact or injured skin. Due to these physical and chemical properties, U toxicity results from both chemical and radiological toxicity. The aim of this work was to find biological markers of internal contamination able to discriminate between chemotoxic and radiotoxic effects of U. The study was carried out in vitro on mouse C3H10T1/2 embryo fibroblasts contaminated either with 0.3% depleted uranium in isotope 235U (DU) or with 12% enriched uranium in isotope 235U (EU). In our experimental conditions, EU has a specific activity 20 times higher than DU. Fibroblasts were grown in culture medium containing various concentrations of DU or EU (0µM, 5µM, 50µM, 500µM and 1000µM). Genotoxic effects of both DU and EU were assessed with the cytokinesis-block micronucleus assay in combination with the fluorescent in situ hybridization of centromeric DNA probes. Binucleated cells with one micronucleus (BN-1MN), binucleated cells with centromere-negative micronucleus (BN-MNC-), mononucleated cells with one MN (Mono-1MN) and nucleoplasmic bridges (NPBs) were scored. Moreover ?-H2AX immunostaining was achieved to detect DNA double-strand breaks (DSB). The percentage of BN-1MN increased with both DU and EU concentration. The percentage of BN-MNC- was significantly higher when cells were contaminated with EU compared to DU for all concentrations (for example, 1,2% and 0,4% for a 50µM EU and DU concentration, respectively), this result confirms clastogen effect of EU. The frequency of NPBs increased with the U concentration. However EU induces more NPBs than DU (for example, 1,35% and 0,25% for a 50µM EU or DU concentration, respectively). In addition, the percentage of Mono-1MN is higher after a contamination with EU compared to DU (for example, 5,5% and 4,5% for a 50µM EU and DU concentration, respectively). The percentage of cells with DSB increased with U concentration. As a conclusion, our experiments show that BN-1MN and DSB seem to be a marker of U genotoxicity (chemical + radiological). The BN-MNC-, NPBs, and to a lesser extent Mono-1MN seem to be a marker of a radiotoxic effect. A microdosimetric calculation is in process and will consolidate these results

Le césium 137 un perturbateur de la fonction physiologique?

National audienceToday, radiation protection is a major issue for the nuclear industry throughout the world, particularly in France. The 2011 disaster of Fukushima Dai-ichi has brought back to public attention questions about the risks associated with nuclear power for civilian purposes. The risk of accidental release of radioactive molecules, including cesium-137 (137Cs), from these facilities cannot be completely eliminated. The non-cancer-related health consequences of chronic exposure to this radionuclide remain poorly understood. After absorption, cesium is distributed throughout the body. The toxicity of 137Cs is due mainly to its radiological properties. Studies in humans report that 137Cs impairs the immune system and induces neurological disorders. Children appear more susceptible than adults to its toxic effects. In animals, and most particularly in rodents, low-dose internal contamination disrupts the sleep-wake cycle, but without behavioural disorders. Impairment of the cardiovascular system has also been observed. Physiologic systems such as the metabolism of vitamin D, cholesterol and steroid hormones are altered, although without leading to the emergence of diseases with clinical symptoms. Recently, a metabolomics study based on contamination levels comparable to those around Chernobyl after the accident showed that it is possible to identify individual rats chronically exposed to low doses of 137Cs, even though the exposure was too low to affect the standard clinical markers. In conclusion, the scientific evidence currently available, particularly that from experimental animal models exposed to chronic contamination, suggests that 137Cs is likely to affect many physiologic and metabolic functions. Thus, it could contribute, with other artificial substances in the environment, to increasing the risk of developing non-cancer diseases in some regions.Aujourd’hui, dans le monde et particulièrement en France, la radioprotection est devenue un des enjeux majeurs pour la filière nucléaire. En effet, la catastrophe de Fukushima Daichi en 2011 a fait ressurgir une nouvelle fois les interrogations sur le risque lié au nucléaire civil. Le risque de rejet accidentel de molécules radioactives, notamment le césium 137 ( 137Cs), ne peut pas être totalement éliminé au niveau de telles installations. Les conséquences sanitaires postaccidentelles d’une exposition chronique à ce radionucléide en termes d’effets biologiques non cancéreux restent encore mal connues. Après absorption, 137Cs se distribue de façon homogène dans l’organisme et sa toxicité résulte essentiellement de ses propriétés radiologiques. Des études chez l’homme ont rapporté que le 137Cs induit une atteinte du système immunitaire, des malformations congénitales ainsi que des troubles neurologiques. Il semblerait aussi que les enfants soient plus sensibles aux effets toxiques du 137Cs que les adultes. Chez l’animal, et plus particulièrement chez le rongeur, une contamination interne à faible dose par le 137Cs entraîne des perturbations du cycle veille-sommeil, mais sans troubles comportementaux. Une atteinte du système cardiovasculaire a également été observée. Des systèmes physiologiques tels que les métabolismes de la vitamine D, du cholestérol et des hormones stéroïdiennes sont modifiés, mais sans l’apparition de pathologies avec symptomatologie clinique. Récemment, une étude métabolomique basée sur des niveaux de contamination postaccidentelle comparable à celle de l’environnement proche de Tchernobyl ont permis de montrer qu’il était possible d’identifier des rats contaminés chroniquement par de faibles doses de 137Cs, alors que les taux de marqueurs cliniques classiques n’étaient pas affectés. En conclusion, les données scientifiques actuellement disponibles, et plus particulièrement les données décrites sur des modèles expérimentaux, après contamination chronique, suggèrent que le 137Cs est susceptible d’affecter de nombreuses fonctions physiologiques et métaboliques. Ainsi, il pourrait contribuer, avec d’autres substances artificielles présentes dans l’environnement, à l’augmentation des risques d’apparition de pathologies non cancéreuses dans certaines régions du globe

Biokinetics of 90Sr after chronic ingestion in a juvenile and adult mouse model

The aim of our study was to define the biokinetics of 90Sr after chronic contamination by ingestion using a juvenile and adult murine model. Animals ingested 90Sr by drinking water containing 20 kBq l -1 of 90Sr. For the juvenile model, parents received 90Sr before mating and their offspring were killed between birth and 20 weeks of ingestion. For the adult model, 90Sr ingestion started at 9 weeks of age and they were killed after different ingestion periods up to 20 weeks. The body weight, food and water consumption of the animals were monitored on a weekly basis. Before killing and sampling of organs, animals were put in metabolic cages. 90Sr in organs and excreta was determined by liquid scintillation \textgreekb counting. Highest 90Sr contents were found in bones and were generally higher in females than in males, and 90Sr retention varied according to the skeletal sites. An accumulation of 90Sr in the bones was observed over time for both models, with a plateau level at adult age for the juvenile model. The highest rate of 90Sr accumulation in bones was observed in early life of offspring, i.e. before the age of 6 weeks. With the exception of the digestive tract, 90Sr was below the detection limit in all other organs sampled. Overall, our results confirm that 90Sr mainly accumulates in bones. Furthermore, our results indicate that there are gender- and age-dependent differences in the distribution of 90Sr after low-dose chronic ingestion in the mouse model. These results provide the basis for future studies on possible non-cancerous effects during chronic, long-term exposure to 90Sr through ingestion in a mouse model, especially on the immune and hematopoietic systems. © 2011 Springer-Verlag

Antioxidant status in rat kidneys after coexposure to uranium and gentamicin

International audienceUranium (U) accumulates and produces its toxic effects preferentially in the kidneys, especially in the proximal tubular structure. U disturbs the balance of pro-/antioxidants in the renal cortex after acute exposure. Other nephrotoxic agents, such as medications, also cause oxidative stress, but the effects of coexposure are not known. The aim of this study was to analyze the effect of chronic exposure to U and acute gentamicin treatment on the pro- and antioxidant status of the renal cortex of rats. Animals were chronically exposed (9 months) to a nonnephrotoxic level of U (40 mg/L) and then treated with daily injections of gentamicin at a range of doses (0, 5, 25, 100, and 150 mg/kg) during the last week of contamination. We studied changes in the gene expression, protein expression, and enzyme activity of key factors involved in the pro-/antioxidant balance in the renal cortex. At and above a dose of 100 mg/kg, gentamicin decreased the messenger RNA (mRNA) levels of catalase (CAT), copper/zinc superoxide dismutase (SOD) and increased the mRNA levels of heme oxygenase-1 in contaminated rats. This treatment decreased CAT activity, but did not significantly change the SOD protein level. Chronic exposure to U did not worsen these effects in our experimental conditions. In conclusion, gentamicin treatment disturbed the oxidative balance in our model's renal cortex, but the chronic exposure to U at this nonnephrotoxic level did not appear to reinforce these effects. © The Author(s) 2013

Testicular steroidogenesis is not altered by 137 cesium Chernobyl fallout, following in utero or post-natal chronic exposure

The testis is especially sensitive to pollutants, including radionuclides. Following the Chernobyl nuclear power plant accident, several of these radionuclides were emitted and spread in the environment. Subsequently, children presented some disruptions of the endocrine system. To determine whether these disruptions were due to 137 cesium(137Cs) exposure, the effects of chronic contamination with low doses of 137Cs in utero or from birth on testicular steroidogenesis in rats were studied. Contamination was continued for 9 months. No modification was observed in circulating level of hormones (17β-estradiol, testosterone, follicle-stimulating hormone, luteinizing hormone) following in utero or post-natal contamination. Expression of several genes involved in testicular steroidogenesis was affected (cyp19a1, fxr, sf-1), without modification of protein expression or activity. Our results suggest that growing organismsmay be affected at themolecular level by 137Cs contamination at this post-accidental dose. © 2010 Académie des sciences