Cytotoxicity of Inorganic and Methylated Arsenic Compounds

Abstract

In the present study, we demonstrated the cytotoxic effects of inorganic arsenicals, arsenite and arsenate, and organic arsenic compounds, monomethylarsonic acid (MAA), dimethylarsinic acid (DMAA) and trimethylarsine oxide (TMAO), which are metabolites of inorganic arsenicals in mammalian bodies, using murine peritoneal macrophages in vitro. Inorganic arsenicals, both arsenite and arsenate, were strongly toxic to macrophages, and their concentrations that decreased the number of surviving cells to 50% of that in untreated controls (IC₅₀) was 5 or 500 μM, respectively. These inorganic arsenicals mainly caused necrosis. In contrast, the cytotoxic effects of methylated arsenic compounds were much lower than those of inorganic arsenicals. The IC₅₀ of DMAA was about 5 mM, and MAA and TMAO had no toxicity even at concentrations over 10 mM, and DMAA mainly induced apoptotic cell death. These data imply that methylation of inorganic arsenicals in mammalia play an important role to suppress both severe immunosuppression and inflammatory responses caused by inorganic arsenicals.