title: Cerium oxide nanoparticles induced toxicity in human lung cells: role of ROS mediated DNA damage and apoptosis.
abstract: Cerium oxide nanoparticles (CeO2 NPs) have promising industrial and biomedical applications. In spite of their applications, the toxicity of these NPs in biological/physiological environment is a major concern. Present study aimed to understand the molecular mechanism underlying the toxicity of CeO2 NPs on lung adenocarcinoma (A549) cells. After internalization, CeO2 NPs caused significant cytotoxicity and morphological changes in A549 cells. Further, the cell death was found to be apoptotic as shown by loss in mitochondrial membrane potential and increase in annexin-V positive cells and confirmed by immunoblot analysis of BAX, BCl-2, Cyt C, AIF, caspase-3, and caspase-9. A significant increase in oxidative DNA damage was found which was confirmed by phosphorylation of p53 gene and presence of cleaved poly ADP ribose polymerase (PARP). This damage could be attributed to increased production of reactive oxygen species (ROS) with concomitant decrease in antioxidant "glutathione (GSH)" level. DNA damage and cell death were attenuated by the application of ROS and apoptosis inhibitors N-acetyl-L-cysteine (NAC) and Z-DEVD-fmk, respectively. Our study concludes that ROS mediated DNA damage and cell cycle arrest play a major role in CeO2 NPs induced apoptotic cell death in A549 cells. Apart from beneficial applications, these NPs also impart potential harmful effects which should be properly evaluated prior to their use.
authors.affiliation: Academy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India ; Nanomaterial Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box 80, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh 226001, India.
authors.forename: Sandeep
authors.identifier: 0000-0003-4616-1064
authors.initials: S
authors.lastname: Mittal
authors.affiliation: Academy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India ; Nanomaterial Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box 80, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh 226001, India.
authors.forename: Alok K
authors.initials: AK
authors.lastname: Pandey
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002563:Cerium / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D004249:DNA Damage; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D002563:Cerium; C030583:ceric oxide; D000111:Acetylcysteine