Cellular Uptake of Trivalent Arsenite and Pentavalent Arsenate in KB Cells Cultured in Phosphate-Free Medium

Abstract

Trivalent arsenite (As(III)) and pentavalent arsenate (As(V)) have been shown to have differential uptake mechanisms. In regular RPMI 1640 medium, As(III) was about 40-fold more toxic to KB oral epidermoid carcinoma cells. However, the cytotoxicity and intracellular accumulation of As(V) were dramatically enhanced, equalling those of As(III) when cells were grown in phosphate-free RPMI medium, As(V) uptake was dose-dependently inhibited by phosphate, mersalyl acid (a membrane sulfhydryl agent), and energy poisons, such as sodium azide and potassium cyanide. These results suggest that As(V) and phosphate share a common transport system. In contrast, As(III) uptake was not affected by the above agents. However, the initial uptake rates of As(III) were linearly correlated with its extracellular concentrations, suggesting that As(III) uptake is probably accomplished through simple diffusion. Our results also show that As(III) and As(V) are excreted from KB cells at a comparable rate, and at least half of As(V) is reduced to the more toxic As(III) prior to excretion into the medium. Therefore, the toxicity of As(V) may in part result from its reduction to As(III).