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.

Keywords: Apoptosis; Arsenic trioxide; Genotoxicity; Oxidative stress; Paradoxical effect; Sodium arsenite.