ARSENATE TOXICITY IN HUMAN ERYTHROCYTES - CHARACTERIZATION OF MORPHOLOGIC CHANGES AND DETERMINATION OF THE MECHANISM OF DAMAGE

Chronic arsenic exposure is associated with alterations in peripheral circulation and vascular disease. Toxicity to the vasculature is docum ented, but the effect of arsenic on the erythrocyte has not been evalu ated. To determine if arsenic was toxic to human erythrocytes and whet her this could contribute to vascular disease, human erythrocytes were incubated in vitro with sodium arsenate, As(V), or sodium arsenite, A s(III), and assessed for damage. After 5 h of incubation with 10 mM As (V) or As(III), significant cell death (hemolysis) only occurred in th e As(V) treated cells. Morphologic changes were assessed by scanning e lectron microscopy and light microscopy. As(V) induced a classic disco cyte-echinocyte transformation extending to the formation of sphero-ec hinocytes; these changes were concentration dependent. As(III) treatme nt also resulted in echinocyte formation but less extensive than in As (V) treated cells, and no sphero-echinocytes were formed. The observed damage was consistent with reported changes induced by ATP depletion, and measurement of ATP in these samples confirmed this as a mechanism of damage. As(V) treatment at concentrations as low as 0.01 mM for 5 h significantly depleted ATP, and As(III) was relatively ineffective i n causing ATP depletion. Based on these three parameters, the erythroc yte was estimated to be as much as 1000 times more susceptible to As(V ) than As(III). ATP is required for the cell to maintain membrane inte grity and deform efficiently in circulation. The changes described her e could contribute to vascular occlusion, ischemia, and tissue death a ssociated with arsenic circulatory disorders.