title: Comparative cytotoxicity of fourteen trivalent and pentavalent arsenic species determined using real-time cell sensing.
abstract: 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. IC50values for the arsenicals were determined continuously over the exposure time, giving rise to IC50histograms 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 IC50values, 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 DMMTAVcoincided 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.
authors.affiliation: Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2G3, Canada; Alberta Centre for Toxicology, Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Birget
authors.initials: B
authors.lastname: Moe
authors.affiliation: Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
authors.forename: Hanyong
authors.initials: H
authors.lastname: Peng
authors.affiliation: Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
authors.forename: Xiufen
authors.initials: X
authors.lastname: Lu
authors.affiliation: Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2G3, Canada; MOE Key Laboratory of Aquatic Product Safety, School of Marine Sciences, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Baowei
authors.initials: B
authors.lastname: Chen
authors.affiliation: Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2G3, Canada; Department of Chemistry, Brock University, St. Catharines, Ontario L2S 3A1, Canada; Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario L8S 4L8, Canada.
authors.forename: Lydia W L
authors.initials: LWL
authors.lastname: Chen
authors.affiliation: Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gabos
authors.affiliation: Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2G3, Canada.
authors.forename: Xing-Fang
authors.initials: XF
authors.lastname: Li
authors.affiliation: Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2G3, Canada. Electronic address: xc.le@ualberta.ca.
authors.forename: X Chris
authors.initials: XC
authors.lastname: Le
mesh_terms: D001151:Arsenic / Q000633:toxicity*; D001152:Arsenicals / Q000009:adverse effects*; D002101:Cacodylic Acid / Q000031:analogs & derivatives; D015386:Hazardous Substances / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D001152:Arsenicals; D015386:Hazardous Substances; C472511:dimethylarsinous acid; C029341:oxophenylarsine; D002101:Cacodylic Acid; C020300:monomethylarsonic acid; D001151:Arsenic
keywords: Arsenic species; Methylarsenicals; Phenylarsenicals; Real-time sensing; Thio-arsenicals; Toxicity