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

作　　者：Birget Moe Hanyong Peng Xiufen Lu Baowei Chen Lydia W.L.Chen Stephan Gabos Xing-Fang Li X.Chris Le 

机构地区：[1]Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry,University of Alberta [2]Alberta Centre for Toxicology, Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary [3]MOE Key Laboratory of Aquatic Product Safety, School of Marine Sciences, Sun Yat-Sen University [4]Department of Chemistry, Brock University [5]Department of Chemistry and Chemical Biology, McMaster University

出　　处：《Journal of Environmental Sciences》2016年第11期113-124,共12页环境科学学报（英文版）

基　　金：supported by Alberta Health, Alberta Innovates, the Canada Research Chairs Program;the Canadian Institutes of Health Research (CIHR);the Natural Sciences and Engineering Research Council (NSERC) of Canada

摘　　要：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.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.

关 键 词：Arsenic species Thio-arsenicals Methylarsenicals Phenylarsenicals Toxicity Real-time sensing 

分 类 号：R114[医药卫生—卫生毒理学]