Interactions of pentavalent and trivalent arsenic with intracellular thiols

Abstract

Trivalent arsenic (As(III)) exposure is linked to cancer, but exposure includes pentavalent arsenic (As(V)). These forms interconvert in biological systems, and the mechanism is not understood. Arsenic has a high affinity for sulfhydryls, and the interaction of As(III) and As(V) with biological sulfhydryls and cellular uptake was investigated in this study. Incubation of rat blood at 1 mM arsenic showed As(V) uptake, membrane and protein binding to be time dependant. These processes were almost immediate with As(III) incubation. Incubation at 25 mM As(V) resulted in 40% thiol depletion with no oxidized glutathione formation. Metabolite analysis showed half of the As(V) converted to As(III). In As(III) incubation, 27% thiol depletion occurred with 300% increase in GSSG. As(V) reduction combined with thiol depletion could indicate that arsenate used sulfhydryls as reducing equivalents. Because arsenate uptake was slow this reduction may not be a main contributor to the overall in vivo process.