Sodium arsenite and arsenic trioxide differently affect the oxidative stress, genotoxicity and apoptosis in A549 cells: An implication for the paradoxical mechanism

• Trivalent inorganic arsenic induced paradoxical effects.
• Paradoxical effects result from cytotoxicity, genotoxicity, oxidative stress and apoptosis.
• Sodium arsenite and arsenic trioxide differential affect multiple biological outcomes.
• Arsenic trioxide is shown to be a more powerful toxic than sodium arsenite.

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.