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Protective and antioxidant role of selenium on arsenic trioxide–induced oxidative stress and genotoxicity in the fish hepatoma cell line PLHC-1

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Abstract

In vitro models are useful tools for rapid screening for toxicity, elucidation of mechanisms of toxicity, and understanding complex interactions among environmental toxicants. These evaluations may provide useful information for ecological evaluations if the relationship between in vitro and in vivo effects is established. The present study was undertaken to evaluate the protective effect of selenium on arsenic trioxide (As2O3)–induced cytotoxicity, DNA damage, and apoptosis. N-acetylcysteine (NAC), a free radical scavenger, was used to determine the involvement of reactive oxygen species (ROS) in As2O3-induced DNA damage and apoptosis. Poeciliopsis lucida hepatocellular carcinoma line 1 (PLHC-1) cells were pretreated with selenium (1, 5, and 10 µM) and NAC (50 and 100 µM) for 2 h. After pretreatment, cells were exposed to 100 µM of As2O3 for 10-, 20-, and 40-h intervals. The As2O3 exposure promoted extensive DNA damage and apoptosis compared to control, while selenium- and NAC-pretreated cells improved cell survival rate against As2O3-induced cell death. Improved survival likely resulted from increasing glutathione peroxidase activity and reduction of ROS formation, reduction of mitochondrial membrane potential damage, DNA damage, and caspase-3 activity. During As2O3 exposure, selenium played the same role as NAC. The authors conclude that As2O3-induced DNA damage and apoptosis are mediated by oxidative stress and selenium and that, although toxic at higher concentrations, selenium provides significant protection against As2O3 effects in PLHC-1 cells. Environ. Toxicol. Chem. 2012; 31: 2861–2869. © 2012 SETAC

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