Differential effects of arsenic on intracellular free calcium levels and the proliferative response of murine mitogen-stimulated lymphocytes

Abstract

This study examined the effects of sodium arsenite treatment on free [Ca 2+]i and cell death in mitogen-activated murine lymphocytes. The main findings of this study were that simultaneous sodium arsenite treatment inhibited PHA- but not Con A-induced T cell proliferation, induced a higher increase in free [Ca 2+]i and an early increase in the proportion of dead cells in PHA than in Con A activated cells. Sodium arsenite pre-treatment reduced both PHA- and Con A-induced T-cell proliferation. Phorbol myristate ester (PMA) did not prevent the inhibitory effects of both sodium arsenite treatments, suggesting that sodium arsenite did not significantly decreased PKC activation or that its effects occurred on events parallel to PKC activation. Both PHA and Con A increased free [Ca 2+]i after stimulation, yet the effect was more pronounced in mitogen-activated cells simultaneously treated with sodium arsenite and particularly in those activated with PHA. The increase in free [Ca 2+]i was in agreement with the early cell death induced by sodium arsenite in PHA-activated cells, a finding consistent with the inhibitory effects on PHA-induced proliferation. Sodium arsenite-induced cell death occurred faster in PHA-activated cells. Further studies are needed to ascertain the relationships between the effects of sodium arsenite on free [Ca 2+]i levels and the type of cell death induced by sodium arsenite and their relevance for the proliferative response of T cells.