The Chernobyl accident released many radionuclides in the environment. Some are still contaminating the ground and thus the people through dietary intake. The long-term sanitary consequences of this disaster are still unclear and several biological systems remain to be investigated. Cholesterol metabolism is of particular interest, with regard to the link established between atherosclerosis and exposure to high-dose ionizing radiations. This study assesses the effect of cesium-137 on cholesterol metabolism in rats, after a chronic exposure since fetal life. To achieve this, rat dams were contaminated with cesium-137-supplemented water from two weeks before mating until the weaning of the pups. Thereafter, the weaned rats were given direct access to the contaminated drinking water until the age of 9 months. After the sacrifice, cholesterol metabolism was investigated in the liver at gene expression and protein level. The cholesterolemia was preserved, as well as the cholesterol concentration in the liver. At molecular level, the gene expressions of ACAT 2 (a cholesterol storage enzyme), of Apolipoprotein A-I and of RXR (a nuclear receptor involved in cholesterol metabolism) were significantly decreased. In addition, the enzymatic activity of CYP27A1, which catabolizes cholesterol, was increased. The results indicate that the rats seem to adapt to the cesium-137 contamination and display modifications of hepatic cholesterol metabolism only at molecular level and within physiological range.
The occurrence of uranium in the environment results from both natural and human origins. Its enrichment in nuclear power plants produces two compounds: enriched uranium (EU) and depleted uranium (DU). The dispersion of uranium in the environment sets human populations at risk of being contaminated mainly through ingestion. After entering the body, uranium builds up in several organs including the brain, where it can induce behaviour disorders after chronic contamination. Brain is the most lipidic organ of the body: half of its weight is due to phospholipids and it contains about 25% of the bodys cholesterol. Cholesterol is essential to brain function due to its various roles, ranging from membrane structure and myelin sheath constitution to synthesis of active molecules such as neurosteroids. Moreover, it is well known that some disruptions in cholesterol metabolism are involved in neurological pathologies, such as Alzheimers disease or Niemann-Pick C disease. Considering the importance of cerebral cholesterol and the susceptibility of brain to uranium exposure, we studied the effect of uranium contamination on cerebral cholesterol metabolism. Therefore, rats were exposed during 9 months to DU through drinking water at a concentration of 40 mg/l (twice the highest environmental level, equivalent to 1 mg/rat/day). After DU contamination, the HDL-cholesterol level in plasma decreased (25%) whereas plasma level of 27-hydroxycholesterol increased (200%). The mRNA levels of several proteins involved in cerebral cholesterol metabolism were modified. Gene expression of CYP46A1, involved in cholesterol catabolism, was increased by 39%. HMGCoA Synthase (HMGS) mRNA levels rose from 91%. Gene expression of three proteins involved in cholesterol transport was also modified: SR-B1 (+34%), ABC A1 (+34%) and Apo E (+75%). Finally, mRNA levels of nuclear receptors PPAR? and PPAR? were increased (46% and 36% respectively). Conversely, gene expression of RXR was reduced by 29%. DU contamination enhances at the same time pathways that increase the cholesterol pool in the cell (uptake and synthesis) and pathways that lead cholesterol out of the cell (detoxification and efflux). This would lead to an overall balanced cholesterol pool in the brain: whatever pathways are primarily altered by DU, the compensatory pathways are also activated. Besides, it is noteworthy that the modification of HDL-cholesterol and 27-hydroxycholesterol plasma levels might foreshadow a disruption of cholesterol metabolism at body level.
The aim of this work was to evaluate and follow up the evolution of radiation damage in two victims of a radiation accident. Blood samples were used for cytogenetic evaluation of radiation dose and heterogeneity. The radiation dose estimates were 1 Gy and 2.3 Gy in the two most exposed patients. Plasma was used for the measurement of the Flt3 ligand as a marker of haematopoietic aplasia, citrulline for damage to the jejunal mucosal epithelium and oxysterols for damage to the liver, the central nervous system and the vascular compartment. The use of these biological indicators demonstrated the presence of a haematopoietic syndrome and suggested the presence of subclinical radiation-induced damage to the liver in one of the two patients. These results support the interest in using these biological indicators in order to evaluate radiation damage, especially in complex accidental situations.
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