Comparative cytotoxicity of fourteen trivalent and pentavalent arsenic species determined using real-time cell sensing

The occurrence of a large number of diverse arsenic species in the environment and in biological systems makes it important to compare their relative toxicity. The toxicity of arsenic species has been examined in various cell lines using different assays, making comparison difficult. We report real-time cell sensing of two human cell lines to examine the cytotoxicity of fourteen arsenic species： arsenite（As~Ⅲ）, monomethylarsonous acid（MMA~Ⅲ） originating from the oxide and iodide forms, dimethylarsinous acid（DMA~Ⅲ）, dimethylarsinic glutathione（DMAG~Ⅲ）, phenylarsine oxide（PAO~Ⅲ）, arsenate（AsV）, monomethylarsonic acid（MMA~Ⅴ）, dimethylarsinic acid（DMA~Ⅴ）,monomethyltrithioarsonate（MMTTA~Ⅴ）, dimethylmonothioarsinate（DMMTA~Ⅴ）,dimethyldithioarsinate（DMDTA~Ⅴ）, 3-nitro-4-hydroxyphenylarsonic acid（Roxarsone, Rox）,and 4-aminobenzenearsenic acid（p-arsanilic acid, p-ASA）. Cellular responses were measured in real time for 72 hr in human lung（A549） and bladder（T24） cells. IC50 values for the arsenicals were determined continuously over the exposure time, giving rise to IC50 histograms and unique cell response profiles. Arsenic accumulation and speciation were analyzed using inductively coupled plasma-mass spectrometry（ICP-MS）. On the basis of the 24-hr IC50 values, the relative cytotoxicity of the tested arsenicals was in the following decreasing order： PAO~Ⅲ？ MMA~Ⅲ≥ DMA~Ⅲ≥ DMAG~Ⅲ≈ DMMTA~Ⅴ≥ As~Ⅲ？ MMTTA~Ⅴ〉 AsV〉 DMDTA~Ⅴ〉DMA~Ⅴ〉 MMA~Ⅴ≥ Rox ≥ p-ASA. Stepwise shapes of cell response profiles for DMA~Ⅲ, DMAG~Ⅲ,and DMMTA~Ⅴcoincided with the conversion of these arsenicals to the less toxic pentavalent DMA~Ⅴ. Dynamic monitoring of real-time cellular responses to fourteen arsenicals provided useful information for comparison of their relative cytotoxicity.

Methylated and thiolated arsenic species for environmental and health research——A review on synthesis and characterization

Hundreds of millions of people around the world are exposed to elevated concentrations of inorganic and organic arsenic compounds, increasing the risk of a wide range of health effects. Studies of the environmental fate and human health effects of arsenic require authentic arsenic compounds. We summarize here the synthesis and characterization of more than a dozen methylated and thiolated arsenic compounds that are not commercially available. We discuss the methods of synthesis for the following14 trivalent（Ⅲ） and pentavalent（） arsenic compounds： monomethylarsonous acid（MMA~Ⅲ）, dicysteinylmethyldithioarsenite（MMA~Ⅲ（Cys）_2）, monomethylarsonic acid（MMA~Ⅴ）,monomethylmonothioarsonic acid（MMMTAⅤ） or monothio-MMA~Ⅴ, monomethyldithioarsonic acid（MMDTA~Ⅴ） or dithio-MMA~Ⅴ, monomethyltrithioarsonate（MMTTA~Ⅴ） or trithio-MMA~Ⅴ,dimethylarsinous acid（DMA~Ⅲ）, dimethylarsino-glutathione（DMA~Ⅲ（SG））, dimethylarsinic acid（DMA~Ⅴ）, dimethylmonothioarsinic acid（DMMTA~Ⅴ） or monothio-DMAⅤ, dimethyldithioarsinic acid（DMDTA~Ⅴ） or dithio-DMA~Ⅴ, trimethylarsine oxide（TMAO~Ⅴ）, arsenobetaine（AsB）, and an arsenicin-A model compound. We have reviewed and compared the available methods,synthesized the arsenic compounds in our laboratories, and provided characterization information. On the basis of reaction yield, ease of synthesis and purification of product, safety considerations, and our experience, we recommend a method for the synthesis of each of these arsenic compounds.