Cellular transport of uranium and its cytotoxicity effects on CHO-k1 cells

Abstract

Uranium is a radioactive heavy metal and a significant public health concern; however, its associated underlying toxicological mechanisms remain largely unknown. In this work, the uptake and efflux processes of uranium in CHO-k1 cells were studied and the cytotoxicity effects were explored. It was found that both the uptake and efflux processes took place rapidly and half of the internalized uranium was expelled within 8 h. The uranium exposure caused a decrease of cell viability and adhesion ability in a dose-dependent manner and blocked the cell cycle at the G1 stage. In addition, gene expression analysis revealed relative changes in the transcription of metabolism related genes. Further studies revealed that the cytotoxicity of uranium could be alleviated by exposing cells to a lower temperature or by the addition of amantadine-HCl, an endocytosis inhibitor. Interestingly, after uranium exposure, needle-like precipitates were observed in both intracellular and extracellular regions. These findings collectively suggest that the cellular transport of uranium is a rapid process that disturbs cell metabolism and induces cytotoxicity, and this impact could be reduced by slowing down endocytic processes.

Keywords

• Uranium
• Cytotoxicity
• Uptake
• Efflux
• Precipitates