Effects of Cysteine on the Cytotoxicity of Arsenic Compounds

Abstract

Effects of cysteine on the cytotoxicity of arsenic compounds, such as arsenite, arsenate, methylarsonic acid (MMA), and dimethylarsinic acid (DMA), were investigated in cultured human HL-60 cells. Using adenosine triphosphate bioluminescence assay, the rank order of the mixtures of arsenicals with cysteine was: DMA > arsenite > arsenate > MMA. The IC₅₀ of DMA with equimolar cysteine was approximately 7.7 μM, nearly two orders of magnitude lower than that of DMA alone. Apoptotic cells were examined by the TUNEL method, and cysteine was found to enhance the induction of apoptosis by arsenicals. Using LC-ICP-MS, trivalent arsenic was detected in the mixtures of arsenate, DMA, and MMA with cysteine. These results suggested that the trivalent arsenic in the mixtures of arsenicals with cysteine might account for the enhanced cytotoxicity as well as apoptosis, and that cysteine is involved in induction of the adverse effects of arsenicals in humans.