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A rostro-caudal gradient of uranium (U) in the brain has been suggested after its inhalation. To study the factors influencing this mapping, we first used 30-min acute inhalation at 56 mg/m3of the relatively soluble form UO4in the rat. These exposure parameters were then used as a reference in comparison with the other experimental conditions. Other groups received acute inhalation at different concentrations, repeated low dose inhalation of UO4(10 exposures) or acute low dose inhalation of the insoluble form UO2. At 24 h after the last exposure, all rats showed a brain U accumulation with a rostro-caudal gradient as compared to controls. However, the total concentration to the brain was greater after repeated exposure than acute exposure, demonstrating an accumulative effect. In comparison with the low dose soluble U exposure, a higher accumulation in the front of the brain was observed after exposure to higher dose, to insoluble particles and following repetition of exposures, thus demonstrating a dose effect and influences of solubility and repetition of exposures. In the last part, exposure to ultrafine U particles made it possible to show 24 h after exposure the presence of U in the brain according to a rostro-caudal gradient. Finally, the time-course after exposure to micronic or nanometric U particles has revealed greater residence times for nanoparticles.

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.

International audience; Uranium nanoparticles (

International audience; Reports have described apparent biological effects of Cs-137 (the most persistent dispersed radionuclide) irradiation in people living in Chernobyl-contaminated territory. The sensitive analytical technology described here should now help assess the relation of this contamination to the observed effects. A rat model chronically exposed to Cs-137 through drinking water was developed to identify biomarkers of radiation-induced metabolic disorders, and the biological impact was evaluated by a metabolomic approach that allowed us to detect several hundred metabolites in biofluids and assess their association with disease states. After collection of plasma and urine from contaminated and non-contaminated rats at the end of the 9-months contamination period, analysis with a LC-MS system detected 742 features in urine and 1309 in plasma. Biostatistical discriminant analysis extracted a subset of 26 metabolite signals (2 urinary, 4 plasma non-polar, and 19 plasma polar metabolites) that in combination were able to predict from 68 up to 94% of the contaminated rats, depending on the prediction method used, with a misclassification rate as low as 5.3%. The difference in this metabolic score between the contaminated and non-contaminated rats was highly significant (P = 0.019 after ANOVA cross-validation). In conclusion, our proof-of-principle study demonstrated for the first time the usefulness of a metabolomic approach for addressing biological effects of chronic low-dose contamination. We can conclude that a metabolomic signature discriminated Cs-137-contaminated from control animals in our model. Further validation is nevertheless required together with full annotation of the metabolic indicators.

The aim of this work was to determine the possible occurrence of damage to the immune system during the course of chronic ingestion of 137Cs. BALB/C mice were used, with 137Cs intake via drinking water at a concentration of 20kBql-1. Adults received 137Cs before mating and offspring were sacrificed at various ages between birth and 20 weeks. Phenotypic analysis of circulating blood cells and thymocytes did not show any significant modification of immune cell populations in animals ingesting 137Cs as compared with control animals, with the exception of a slight increase in Treg percentage at the age of 12weeks. Functional tests, including proliferative response to mitogens such as phytohaemagglutinin, response to alloantigens in mixed lymphocyte reaction and immunoglobulin response to vaccine antigens such as tetanus toxin and keyhole limpet haemocyanin did not show any significant functional modification of the immune system in 137Cs-ingesting animals as compared with control animals. Overall, our results suggest that chronic ingestion of a low concentration of 137Cs in drinking water in the long term does not have any biologically relevant effect on the immune system. © 2011 IOP Publishing Ltd.

The aim of this work was to compare the distribution of 137Cs in organisms after chronic ingestion following different schedules. Rats were contaminated through drinking water containing 6,500 Bq L-1 of 137Cs, starting either at birth, at weaning, or upon reaching adult age (13 wk). Animals were then sacrificed after different durations of ingestion. 137Cs content of organs and excreta were determined by γ counting. A slight decrease in Cs elimination through urine was observed according to the age of animals. All organs tested showed similar 137Cs content, with the exception of striated muscles and the thyroid at certain ages, which showed the highest accumulation of Cs. The lowest 137Cs concentration was found in the blood, which acts as a transfer compartment after absorption in the intestine. Substructures of the central nervous system showed a homogeneous level of 137Cs accumulation, except for the olfactive bulbs. In these structures, an increased concentration of 137Cs was observed, suggesting a possible direct route of intake through the nasal epithelium. Overall, these results are in agreement with current models for the biokinetics of 137Cs. However, these results also suggest that the thyroid should be taken into account in future models of 137Cs biokinetics. Copyright © 2010 Health Physics Society.

The aim of this work was to define the possible occurrence of hematological changes during the course of a chronic ingestion of 137Cs. A mouse model was used, with ingestion through drinking water with a cesium concentration of 20 kBq l -1. Ingestion started in parent animals before mating, and 137Cs intake and its effect on the hematopoietic system was studied in offspring at various ages between birth and 20 weeks. 137Cs content was measured in various organs, indicating that 137Cs was distributed throughout the organism including lymphohematopoietic organs, i.e., femurs, spleen and thymus. However, we did not observe any effect on the hematopoietic system, whatever the parameter used. In fact, blood cell counts, mononuclear cell counts and progenitor frequency in bone marrow and spleen, and Flt3-ligand, Erythropoietin, G-CSF and SDF-1 concentration in plasma remained unchanged when compared to control animals. Moreover, phenotypic analysis did not show any change in the proportions of bone marrow cell populations. These results indicate that, although 137Cs was found in all organs implicated in the hematopoietic system, this did not induce any changes in bone marrow function. © Springer-Verlag 2010.

Uranium uptake can occur accidentally by inhalation, ingestion, injection, or absorption through intact or wounded skin. Intact or wounded skin routes of absorption of uranium have received little attention. The aims of our work were (1) to evaluate the influence of the type of wound contamination on the short term distribution and excretion of uranium in rats and (2) to generate data to assess the time available to treat contamination of intact or wounded skin before significant uptake of uranium occurs. Biokinetic data presented in the present paper are based on an in vivo rat model. This study shows that a significant uptake of a uranyl nitrate solution through intact skin can occur within the first 6 h of exposure. Absorption of a uranyl nitrate solution through excoriated skin is significant after only 30 min of exposure. After a 24-h exposure, uranium uptake through intact skin and excoriated skin represents about 0.4% and 38% of the initial deposit of uranium, respectively. Contaminated serious chemical skin burns induced by HNO3 or NaOH are paradoxically less important in terms of uranium uptake risk because 99% of the incorporated uranium remains trapped at the wound site and its incorporation is delayed for at least 6 h after the beginning of contamination. These results confirm that the biokinetics of a given physicochemical form of uranium incorporated after wound contamination depend largely on the physiological evolution of the considered wound. Each type of wound, with its corresponding biokinetics of a uranium species, is a particular case. ©2007Health Physics Society.

Since the Chernobyl accident, the most significant problem for the population living in the contaminated areas is chronic exposure by ingestion of radionuclides, notably 137Cs, a radioactive isotope of cesium. It can be found in the whole body, including the central nervous system. The present study aimed to assess the effect of 137Cs on the central nervous system and notably on open-field activity and the electroencephalographic pattern. Rats were exposed up to 90 days to drinking water contaminated with 137Cs at a dosage of 400 Bq kg-1, which is similar to that ingested by the population living in contaminated territories. At this level of exposure, no significant effect was observed on open-field activity. On the other hand, at 30 days exposure, 137Cs decreased the number of episodes of wakefulness and slow wave sleep and increased the mean duration of these stages. At 90 days exposure, the power of 0.5-4 Hz band of 137Cs-exposed rats was increased in comparison with controls. These electrophysiological changes may be due to a regional 137Cs accumulation in the brain stem. In conclusion, the neurocognitive effects of 137Cs need further evaluation and central disorders of population living in contaminated territories must be considered. © 2006 Elsevier Ireland Ltd. All rights reserved.