Arsenite efflux is inhibited by verapamil, cyclosporin A, and GSH-depleting agents in arsenite-resistant Chinese hamster ovary cells.

We have previously demonstrated that arsenite-resistant SA7 cells can extrude arsenite more effectively and completely than their parental Chinese hamster ovary cells. Our present results show that arsenite efflux from SA7 cells is inhibited by chemosensitizing agents to multidrug resistant-associated protein: verapamil and cyclosporin A and by glutathione-depleting agents: dinitrofluorobenzene and diethyl maleate. These results suggest that arsenite extrusion in SA7 cells may be mediated by a GSH-dependent and verapamil- and cyclosporin A-sensitive membrane transport system. Since arsenite extrusion was found dose-dependently inhibited by energy poison [potassium cyanide (KCN)] and an ATPase inhibitor (sodium vanadate), ATP is apparently required for arsenite extrusion in SA7 cells.