Toxicity of uranium on renal cells

Kidney and bone are the main retention organs affected by uranium toxicity. Although the clinical effects of uranium poisoning are well known, only few studies dealt with cellular mechanisms of toxicity. The purpose of this study was to investigate the cyto- and genotoxicity of uranium (U) on renal cells. The cell death was also studied in this conditions of exposure. The effects of U were evaluated in acute and chronic exposure. The acute effects were evaluated after 24 h exposure to strong U concentrations (200-700μM). The chronic exposure was observed on renal cells incubated with low U concentrations (0.1-100 μM) until 70 days then with high uranium concentrations (400-500 μM) during 24 h. U induces apoptosis cell death mainly by the intrinsic pathway. The high U concentrations (600-700 μM) lead to necrosis. U induces DNA damages (single, double strand breaks, as well as alkali labile sites) from 300μM. The cytotoxicity and intracellular accumulation of uranium were less important in cells previously exposed to low uranium concentrations when compared to non-exposed cells. In the same time, DNA damage observed after acute exposure of uranium decreased with the increase of chronic uranium concentrations. These results suggest that renal cells became resistant to uranium, probably due to a cellular transformation process. In conclusion, high U concentrations (300-700μM) induce apoptosis cell death and DNA damages. Cells previously exposed to low U concentrations present also DNA damages and a cellular transformation. (authors)