title: Nickel oxide nanoparticles induce inflammation and genotoxic effect in lung epithelial cells.
abstract: Nickel oxide nanoparticles (NiONPs) toxicity has been evaluated in the human pulmonary epithelial cell lines: BEAS-2B and A549. The nanoparticles, used at the doses of 20, 40, 60, 80, 100 μg/ml, induced a significant reduction of cell viability and an increase of apoptotic and necrotic cells at 24h. A significant release of interleukin-6 and -8 was assessed after 24h of treatment, even intracellular ROS increased already at 45 min after exposure. The results obtained evidenced that the cytokines release was dependent on mitogen activated protein kinases (MAPK) cascade through the induction of NF-kB pathway. NiONPs induced cell cycle alteration in both the cell lines even in different phases and these modifications may be induced by the NPs genotoxic effect, suggested by the nuclear translocation of phospho-ATM and phospho-ATR. Our results confirm the cytotoxic and pro-inflammatory potential of NiONPs. Moreover their ability in inducing DNA damage responses has been demonstrated. Such effects were present in A549 cells which internalize the NPs and BEAS-2B cells in which endocytosis has not been observed.
authors: Polaris Research Centre, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milano, Italy. Electronic address: laura.capasso@unimib.it.
authors: Laura
authors: L
authors: Capasso
authors: Polaris Research Centre, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milano, Italy. Electronic address: marina.camatini@unimib.it.
authors: Marina
authors: M
authors: Camatini
authors: Polaris Research Centre, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milano, Italy. Electronic address: gualtieri.maurizio@gmail.com.
authors: Maurizio
authors: M
authors: Gualtieri
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity*; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D009532:Nickel / Q000378:metabolism / Q000633:toxicity*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D009153:Mutagens; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009532:Nickel; C028007:nickel monoxide; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: Interleukins; MAP-kinases; NF-kB; Nickel oxide nanoparticles; Pulmonary epithelial cells; ROS