The aim of this work was to define the possible occurrence of hematological changes during the course of a chronic ingestion of (137)Cs. 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 (137)Cs intake and its effect on the hematopoietic system was studied in offspring at various ages between birth and 20 weeks. (137)Cs content was measured in various organs, indicating that (137)Cs was distributed throughout the organism including lympho-hematopoietic 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 (137)Cs was found in all organs implicated in the hematopoietic system, this did not induce any changes in bone marrow function.

The aim of this work was to characterize multipotent mesenchymal stromal cells (MSCs) in the postnatal human thymus and to localize these MSCs in the organ. Adherent cells isolated from thymus samples were characterized by cell-surface antigen expression. This showed that adherent cells have a MSC profile as assessed by the expression of CD73 and CD105 markers and the lack of CD45 expression. These cells are able to differentiate in vitro into adipocytes, osteoblasts, and chondrocytes and to inhibit mixed lymphocyte reaction. This indicates that isolated cells have all of the characteristics of MSC. The fibroblast colony-forming unit (CFU-F) assay was used to determine their frequency in the postnatal thymus. This frequency was 60.9 +/- 14.8 CFU-F per 1 x 10(5) freshly isolated mononuclear cells. Moreover, taking advantage of CD34 and CD105 expression, immunohistological staining allowed us to localize MSC within interlobular trabeculae in close contact with the outer cortex. Polymerase chain reaction experiments indicated that thymic MSC expressed interleukin-7 and stromal cell-derived factor-1 messenger RNA. Overall, these results confirm previous findings of the presence in the adult human thymus of multipotent MSCs with a phenotype similar to adipose-derived adult stem cells. These results also show for the first time a histological localization of MSC in an organ. This suggests a possible role of thymic MSC in intrathymic differentiation.

The aim of our study was to define the biokinetics of (90)Sr after chronic contamination by ingestion using a juvenile and adult murine model. Animals ingested (90)Sr by drinking water containing 20 kBq l(-1) of (90)Sr. For the juvenile model, parents received (90)Sr before mating and their offspring were killed between birth and 20 weeks of ingestion. For the adult model, (90)Sr 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. (90)Sr in organs and excreta was determined by liquid scintillation β counting. Highest (90)Sr contents were found in bones and were generally higher in females than in males, and (90)Sr retention varied according to the skeletal sites. An accumulation of (90)Sr 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 (90)Sr 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, (90)Sr was below the detection limit in all other organs sampled. Overall, our results confirm that (90)Sr mainly accumulates in bones. Furthermore, our results indicate that there are gender- and age-dependent differences in the distribution of (90)Sr 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 (90)Sr through ingestion in a mouse model, especially on the immune and hematopoietic systems.

A central question in radiation protection research is dose and dose-rate relationship for radiation-induced cardiovascular diseases. The response of endothelial cells to different low dose rates may contribute to help estimate risks for cardiovascular diseases by providing mechanistic understanding. In this study we investigated whether chronic low-dose-rate radiation exposure had an effect on the inflammatory response of endothelial cells and their function. Human umbilical vein endothelial cells (HUVECs) were chronically exposed to radiation at a dose of 1.4 mGy/h or 4.1 mGy/h for 1, 3, 6 or 10 weeks. We determined the pro-inflammatory profile of HUVECs before and during radiation exposure, and investigated the functional consequences of this radiation exposure by measuring their capacity to form vascular networks in matrigel. Expression levels of adhesion molecules such as E-selectin, ICAM-1 and VCAM-1, and the release of pro-inflammatory cytokines such as MCP-1, IL-6 and TNF-α were analyzed. When a total dose of 2 Gy was given at a rate of 4.1 mGy/h, we observed an increase in IL-6 and MCP-1 release into the cell culture media, but this was not observed at 1.4 mGy/h. The increase in the inflammatory profile induced at the dose rate of 4.1 mGy/h was also correlated with a decrease in the capacity of the HUVECs to form a vascular network in matrigel. Our results suggest that dose rate is an important parameter in the alteration of HUVEC inflammatory profile and function.

Uranium is a heavy metal naturally found in the earth's crust that can contaminate the general public population when ingested. The acute effect and notably the uranium nephrotoxicity are well known but knowledge about the effect of chronic uranium exposure is less clear. In a dose-response study we sought to determine if a chronic exposure to uranium is toxic to the kidneys and the liver, and what the anti-oxidative system plays in these effects. Rats were contaminated for 3 or 9 months by uranium in drinking water at different concentrations (0, 1, 40, 120, 400, or 600 mg/L). Uranium tissue content in the liver, kidneys, and bones was linear and proportional to uranium intake after 3 and 9 months of contamination; it reached 6 μg per gram of kidney tissues for the highest uranium level in drinking water. Nevertheless, no histological lesions of the kidney were observed, nor any modification of kidney biomarkers such as creatinine or KIM-1. After 9 months of contamination at and above the 120-mg/L concentration of uranium, lipid peroxidation levels decreased in plasma, liver, and kidneys. Glutathione concentration increased in the liver for the 600-mg/L group, in the kidney it increased dose dependently, up to 10-fold, after 9 months of contamination. Conversely, chronic uranium exposure irregularly modified gene expression of antioxidant enzymes and activities in the liver and kidneys. In conclusion, chronic uranium exposure did not induce nephrotoxic effects under our experimental conditions, but instead reinforced the antioxidant system, especially by increasing glutathione levels in the kidneys.

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