CELLULAR UPTAKE OF TRIVALENT ARSENITE AND PENTAVALENT ARSENATE IN KB CELLS CULTURED IN PHOSPHATE-FREE MEDIUM

Trivalent arsenite (As(III)) and pentavalent arsenate (As(V)) have bee n shown to have differential uptake mechanisms. In regular RPMI 1640 m edium, As(III) was about 40-fold more toxic to KB oral epidermoid carc inoma cells. However, the cytotoxicity and intracellular accumulation of As(V) were dramatically enhanced, equalling those of As(III) when c ells were grown in phosphate-free RPMI medium. As(V) uptake was dose-d ependently inhibited by phosphate, mersalyl acid (a membrane sulfhydry l agent), and energy poisons, such as sodium azide and potassium cyani de. These results suggest that As(V) and phosphate share a common tran sport system. In contrast, As(III) uptake was not affected by the abov e agents. However, the initial uptake rates of As(III) were linearly c orrelated with its extracellular concentrations, suggesting that As(II I) uptake is probably accomplished through simple diffusion. Our resul ts also show that As(III) and As(V) are excreted from KB cells at a co mparable 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 o f As(V) may in part result from its reduction to As(III). (C) 1996 Aca demic Press, Inc.