Main content area

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

Moe, Birget, Peng, Hanyong, Lu, Xiufen, Chen, Baowei, Chen, Lydia W.L., Gabos, Stephan, Li, Xing-Fang, Le, X. Chris
Journal of environmental sciences (China) 2016 v.49 pp. 113-124
arsenates, arsenic, arsenites, atomic absorption spectrometry, bladder, cacodylic acid, cytotoxicity, exposure duration, glutathione, human cell lines, humans, inhibitory concentration 50, iodides, monitoring, roxarsone
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 (Asᴵᴵᴵ), monomethylarsonous acid (MMAᴵᴵᴵ) originating from the oxide and iodide forms, dimethylarsinous acid (DMAᴵᴵᴵ), dimethylarsinic glutathione (DMAGᴵᴵᴵ), phenylarsine oxide (PAOᴵᴵᴵ), arsenate (Asⱽ), monomethylarsonic acid (MMAⱽ), dimethylarsinic acid (DMAⱽ), monomethyltrithioarsonate (MMTTAⱽ), dimethylmonothioarsinate (DMMTAⱽ), dimethyldithioarsinate (DMDTAⱽ), 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, Rox), and 4-aminobenzenearsenic acid (p-arsanilic acid, p-ASA). Cellular responses were measured in real time for 72hr 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: PAOᴵᴵᴵ≫MMAᴵᴵᴵ≥DMAᴵᴵᴵ≥DMAGᴵᴵᴵ≈DMMTAⱽ≥Asᴵᴵᴵ≫MMTTAⱽ>Asⱽ>DMDTAⱽ>DMAⱽ>MMAⱽ≥Rox≥p-ASA. Stepwise shapes of cell response profiles for DMAᴵᴵᴵ, DMAGᴵᴵᴵ, and DMMTAⱽ coincided with the conversion of these arsenicals to the less toxic pentavalent DMAⱽ. Dynamic monitoring of real-time cellular responses to fourteen arsenicals provided useful information for comparison of their relative cytotoxicity.