Carrière M, Avoscan L, Collins R, Carrot F, Khodja H, Ansoborlo E, Gouget B
Laboratoire Pierre Süe CEA-CNRS UMR 9956, 91191 Gif sur Yvette, France.
Chem Res Toxicol. 2004 Mar;17(3):446-52. doi: 10.1021/tx034224h.
Uranium is a naturally occurring heavy metal. Its extensive use in the nuclear cycle and for military applications has focused attention on its potential health effects. Acute exposures to uranium are toxic to the kidneys where they mainly cause damage to proximal tubular epithelium. 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, representative of rat kidney proximal epithelium, 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, uranium cytotoxicity appears after 16 h of exposure. The CI50 cytotoxicity index, the uranium concentration leading to 50% dead cells after 24 h of exposure, is 500 microM (+/-100 microM) and strongly depends on uranyl counterion and cell culture medium composition. Computer modeling of uranyl speciation is reported, enabling one to draw a parallel between uranyl speciation and its cytotoxicity.
铀是一种天然存在的重金属。它在核循环及军事应用中的广泛使用，已使其潜在的健康影响受到关注。急性接触铀对肾脏有毒性，主要会导致近端肾小管上皮受损。本研究的目的是调查急性体外铀酰暴露的生物学后果以及铀酰形态对其细胞毒性的影响。NRK - 52E细胞是大鼠肾近端上皮的代表细胞，将其暴露于碳酸铀酰和柠檬酸铀酰络合物中，这两种络合物是急性体内污染后经肾小管转运的主要络合物。在NRK - 52E细胞暴露前，将这些络合物在经典或改良细胞培养基中稀释，这可能会改变铀酰形态。在这些条件下，铀的细胞毒性在暴露16小时后出现。CI50细胞毒性指数，即暴露24小时后导致50%细胞死亡的铀浓度为500微摩尔（±100微摩尔），且强烈依赖于铀酰抗衡离子和细胞培养基成分。报告了铀酰形态的计算机建模，能够在铀酰形态与其细胞毒性之间建立联系。
