title: Protective and antioxidant role of selenium on arsenic trioxide-induced oxidative stress and genotoxicity in the fish hepatoma cell line PLHC-1.
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 (As(2) O(3) )-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 As(2) O(3) -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 As(2) O(3) for 10-, 20-, and 40-h intervals. The As(2) O(3) exposure promoted extensive DNA damage and apoptosis compared to control, while selenium- and NAC-pretreated cells improved cell survival rate against As(2) O(3) -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 As(2) O(3) exposure, selenium played the same role as NAC. The authors conclude that As(2) O(3) -induced DNA damage and apoptosis are mediated by oxidative stress and selenium and that, although toxic at higher concentrations, selenium provides significant protection against As(2) O(3) effects in PLHC-1 cells.
authors.affiliation: Department of Integrated Science and Technology, Marshall University, Huntington, WV, USA.
authors.forename: Vellaisamy
authors.initials: V
authors.lastname: Selvaraj
authors.forename: Mindy
authors.initials: M
authors.lastname: Yeager-Armstead
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Murray
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D005399:Fishes / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism; D015386:Hazardous Substances / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010087:Oxides / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D001152:Arsenicals; D016166:Free Radical Scavengers; D015386:Hazardous Substances; D009153:Mutagens; D010087:Oxides; D017382:Reactive Oxygen Species; D053148:Caspase 3; D012643:Selenium; D000077237:Arsenic Trioxide; D000111:Acetylcysteine