Cell proliferation and cell death are disturbed during prenatal and postnatal brain development after uranium exposure

International audienceThe developing brain is more susceptible to neurotoxic compounds than adult brain. It is also well known that disturbances during brain development cause neurological disorders in adulthood. The brain is known to be a target organ of uranium (U) exposure and previous studies have noted that internal U contamination of adult rats induces behavioral disorders as well as affects neurochemistry and neurophysiological properties. In this study, we investigated whether depleted uranium (DU) exposure affects neurogenesis during prenatal and postnatal brain development. We examined the structural morphology of the brain, cell death and finally cell proliferation in animals exposed to DU during gestation and lactation compared to control animals. Our results showed that DU decreases cell death in the cortical neuroepithelium of gestational day (GD) 13 embryos exposed at 40. mg/L and 120. mg/L and of GD18 fetuses exposed at 120. mg/L without modification of the number of apoptotic cells. Cell proliferation analysis showed an increase of BrdU labeling in the dentate neuroepithelium of fetuses from GD18 at 120. mg/L. Postnatally, cell death is increased in the dentate gyrus of postnatal day (PND) 0 and PND5 exposed pups at 120. mg/L and is associated with an increase of apoptotic cell number only at PND5. Finally, a decrease in dividing cells is observed in the dentate gyrus of PND21 rats developmentally exposed to 120. mg/L DU, but not at PND0 and PND5. These results show that DU exposure during brain development causes opposite effects on cell proliferation and cell death processes between prenatal and postnatal development mainly at the highest dose. Although these modifications do not have a major impact in brain morphology, they could affect the next steps of neurogenesis and thus might disrupt the fine organization of the neuronal network

Hto, Tritiated Amino Acid Exposure and External Exposure Induce Differential Effects on Hematopoiesis and Iron Metabolism

International audienceThe potential increase in tritium release from either nuclear reactors or new facilities such as the ITER reactor raises questions about the reliability of current ICRP and WHO recommendations about tritium exposure to human populations. In order to study the potential toxicity of tritium at the regulatory level, mice were chronically exposed through drinking water at three concentrations of tritium, 10 kBq.L-1, 1 MBq.L-1 and 20 MBq.L-1, in two different forms, either HTO or tritiated non-essential amino acids (TAA). After one month exposure, a dose-dependent anemia was evidenced, in association with an iron deprivation, in all TAA exposed groups, but not in HTO exposed groups. This anemia was compensated after eight months of exposure through an increase in mean globular volume, demonstrating the occurrence of an iron deficit-associated anemia (IDA). The analysis of hematopoiesis, of red blood cell retention in the spleen and of iron metabolism in the liver, the kidneys and the intestine suggested that the iron deficit was associated with a defect in iron capture in the intestine. By contrast, mice exposed to external gamma irradiation at equivalent dose rate during either one or eight months did not show any change in red blood cells numbers, white blood cells numbers or iron concentration in the plasma. Overall these results demonstrate that health effects may appear with chronic exposure to concentration of tritium above regulatory levels, but these effects are dependent upon the speciation of tritium

Hto, Tritiated Amino Acid Exposure and External Exposure Induce Differential Effects on Hematopoiesis and Iron Metabolism

International audienceThe potential increase in tritium release from either nuclear reactors or new facilities such as the ITER reactor raises questions about the reliability of current ICRP and WHO recommendations about tritium exposure to human populations. In order to study the potential toxicity of tritium at the regulatory level, mice were chronically exposed through drinking water at three concentrations of tritium, 10 kBq.L-1, 1 MBq.L-1 and 20 MBq.L-1, in two different forms, either HTO or tritiated non-essential amino acids (TAA). After one month exposure, a dose-dependent anemia was evidenced, in association with an iron deprivation, in all TAA exposed groups, but not in HTO exposed groups. This anemia was compensated after eight months of exposure through an increase in mean globular volume, demonstrating the occurrence of an iron deficit-associated anemia (IDA). The analysis of hematopoiesis, of red blood cell retention in the spleen and of iron metabolism in the liver, the kidneys and the intestine suggested that the iron deficit was associated with a defect in iron capture in the intestine. By contrast, mice exposed to external gamma irradiation at equivalent dose rate during either one or eight months did not show any change in red blood cells numbers, white blood cells numbers or iron concentration in the plasma. Overall these results demonstrate that health effects may appear with chronic exposure to concentration of tritium above regulatory levels, but these effects are dependent upon the speciation of tritium