Arsenic trioxide (As2O3) induces apoptosis and necrosis mediated cell death through mitochondrial membrane potential damage and elevated production of reactive oxygen species in PLHC-1 fish cell line

作者：Selvaraj Vellaisamy; Armistead Mindy Yeager; Cohenford Menashi; Murray Elizabeth^*

来源：Chemosphere, 2013, 90(3): 1201-1209.

DOI：10.1016/j.chemosphere.2012.09.039

• Arsenic trioxide
• PLHC-1
• Apoptosis
• Necrosis
• p53
• ROS

Several environmental pollutants, including metals can induce toxicological effect on aquatic animal species. Most studies to understand the toxicity of arsenic compounds were performed in mammalian cells; however, the study of the arsenic toxicity to the aquatic animals' species, including fish, is limited. So the objective of this study was first to investigate the effects of As2O3 induced toxicity particularly on apoptosis and necrosis mediated cell death in fish cell PLHC-1 as compared to the mechanism of toxicity from known mammalian cell lines, secondly to relate in vitro effects in fish to those demonstrated by in vivo systems. To conduct this study, PLHC-1 cells were exposed to various concentrations of As2O3 (0-100 mu M) for 10, 20 and 40 h. The results indicate that As2O3 exposure promoted apoptotic and necrotic mediated cell death in a concentration and time dependent manner. Cell death (apoptotic and necrotic) induced by As2O3 was further confirmed by changes in various phases of cell cycle, DNA fragmentation (necro- comet and apo-comet) in the comet assay, alteration in mitochondrial membrane potential and formation of increased reactive oxygen species (ROS). Apoptotic mediated cell death was confirmed further by observing the increased caspase-3 activity and elevated expression of p53, cytochrome c and Bax proteins levels in the same experimental conditions. PLHC-1 cells were shown to be a good model for evaluating biochemical/cytotoxic effects following exposure to various reference chemicals and environmental contaminants. In vitro data obtained from this study provides a comprehensive approach for the elucidating the actual molecular mechanism for As2O3 induced toxicity particularly apoptosis and necrosis mediated cell death in PLHC-1 cell line.

• 出版日期2013-1