title: Sodium arsenite and arsenic trioxide differently affect the oxidative stress, genotoxicity and apoptosis in A549 cells: an implication for the paradoxical mechanism.
abstract: Although arsenic toxicity greatly depends on its chemical forms, few studies have taken into account the paradoxical phenomenon which is manifested by that sodium arsenite (NaAsO₂) acts as a potent carcinogen but arsenic trioxide (As₂O₃) serves as an effective therapeutic agent. In this study, we compared the in vitro effects of NaAsO₂ and As₂O₃ on cell viability, colony formation, cell cycle progression, apoptosis, genotoxicity and oxidative stress in human lung adenocarcinoma A549 cells. Our results demonstrated that both NaAsO₂ and As₂O₃ caused oxidative stress, genotoxicity, cytotoxicity, cell cycle arrest as well as apoptosis, while As₂O₃ induced higher production of reactive oxygen species (ROS) with a more remarkable decrease in superoxide dismutase (SOD) activities and intracellular levels of glutathione (GSH) than NaAsO₂. Moreover, the degree of DNA damage, chromosomal breakage, cell cycle arrest and apoptosis in As₂O₃-treated cells were more severe than those in NaAsO₂-treated cells. These findings suggest that differential effects and mechanisms of NaAsO₂ and As₂O₃ may responsible for the paradoxical effects of arsenic on the carcinogenesis and anticancer function.
authors.affiliation: Department of Environmental Health, West China School of Public Health, Sichuan University, Chengdu 610041, PR China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Jiang
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Zunzhen
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D018053:Arsenites / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004396:Coloring Agents; D020552:Comet Assay; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D020287:In Situ Nick-End Labeling; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017670:Sodium Compounds / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D014410:Tumor Stem Cell Assay
chemical_list: D017304:Annexin A5; D001152:Arsenicals; D018053:Arsenites; D004396:Coloring Agents; D005456:Fluorescent Dyes; D009153:Mutagens; D010087:Oxides; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; C017947:sodium arsenite; D013482:Superoxide Dismutase; C022616:thiazolyl blue; D016650:Fluorescein-5-isothiocyanate; D000077237:Arsenic Trioxide
keywords: Apoptosis; Arsenic trioxide; Genotoxicity; Oxidative stress; Paradoxical effect; Sodium arsenite