Intracellular behaviour of uranium(VI) on renal epithelial cell in culture (LLC-PK1): influence of uranium speciation
Mirto H, Henge-Napoli MH, Gibert R, Ansoborlo E, Fournier M, Cambar J
Toxicol Lett 1999 Feb 22;104(3):249-56
The main objective of this work was to assess the potentiality of in vitro models to study and understand the uranium-induced cytotoxicity on renal cells. Cytotoxicity and morphological studies were performed in a tubular proximal original established cell line (LLC-PK1 cell line). Dose-dependent cytotoxicity response was obtained with the uranium bicarbonate complex. In vitro experiments revealed a toxicity of uranium-bicarbonate complexes after a 24-h exposition and for concentrations ranging from 7 x 10(-4) M to 10(-3) M. In contrast, a lack of cytotoxicity of uranium(VI) citrate complexes studied using the same experimental conditions was noticed. Furthermore, electron transmission microscopy and X-ray microanalysis studies, after exposition of LLC-PK1 cells to the uranium-bicarbonate system ([U] = 8 x 10(-4) M) revealed that uranium entered into the cells and it was precipitated within the cytoplasmic compartment as uranyl phosphate needles. Similar morphological studies conducted with citrate complexes did not show any intake of uranium by LLC-PK1 cells. Experiments conducted in phosphate free culture medium showed that uranium was incorporated as a soluble material and that the association of the metal with phosphate ions occurred in the cytoplasmic compartment of LLC-PK1 cells.