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Influence of uranium speciation on normal rat kidney (NRK-52E) proximal cell cytotoxicity
M. Carrière, L. Avoscan, R. Collins, H. Khodja, , B. Gouget
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Influence of uranium speciation on normal rat kidney (NRK-52E) proximal cell cytotoxicity

Uranyl speciation in cell culture medium simulated with J-Chess softwarea. Uranyl speciation is simulated in classical (MEM) or reconstituted cell culture medium containing various NaHCO3, CaCl2, NaH2PO4 concentrations. Percentage of uranium complexation is detailed, with arrows indicating an increase (↑) or a decrease (↓) in percentage as compared to classical MEM medium. The first line gives the relative cytotoxicity of each uranyl exposure solution obtained experimentally.

Coll. E. Ansoborlo* *CEA VALRHO, DEN/VRH/DRCP/CETA/DIR, BP 17171, 30207 Bagnols sur Cèze, France Uranium is a nephrotoxicant that causes damage to proximal tubular epithelium. Although renal damage consecutive to an acute uranium exposure has been largely studied in vivo, few in vitro studies are documented. In vitro cell systems have been assessed to be pertinent models for mechanistic studies. The normal rat kidney cell line (NRK-52E) is the only non cancerous rat renal proximal tubular epithelial cell model, thus allowing studies on an homogeneous cell system and comparison of in vitro results to in vivo data obtained from rat intoxication. The purpose of this study was to investigate the biological consequences of acute in vitro uranyl exposure and the influence of uranyl speciation on its cytotoxicity. NRK-52E cells were exposed to uranyl-carbonate and -citrate complexes, which are the major complexes transiting through renal tubules after acute in vivo contamination. Before NRK-52E cell exposure, these complexes were diluted in classical or modified cell culture media, which can possibly modify uranyl speciation. In these conditions, the CI50 cytotoxicity index of uranyl is 500 µM (+/- 100 µM) and strongly depends on uranyl counter ion and cell culture medium composition. Computer modelization of uranyl speciation is reported. This study is a first step towards the experimental determination of uranyl speciation. For the first time a parallel is drawn between uranyl speciation and its cytotoxicity and, therefore the determination of cytotoxic uranyl complexes. Such studies will allow the emergence of more effective future decorporation treatments.  
#431 - Last update : 03/25 2005


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