PMID- 24503009 OWN - NLM STAT- MEDLINE DCOM- 20140502 LR - 20190816 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 226 IP - 1 DP - 2014 Apr 7 TI - Nickel oxide nanoparticles induce inflammation and genotoxic effect in lung epithelial cells. PG - 28-34 LID - S0378-4274(14)00060-5 [pii] LID - 10.1016/j.toxlet.2014.01.040 [doi] AB - 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 mug/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. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Capasso, Laura AU - Capasso L AD - Polaris Research Centre, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milano, Italy. Electronic address: laura.capasso@unimib.it. FAU - Camatini, Marina AU - Camatini M AD - Polaris Research Centre, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milano, Italy. Electronic address: marina.camatini@unimib.it. FAU - Gualtieri, Maurizio AU - Gualtieri M AD - Polaris Research Centre, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milano, Italy. Electronic address: gualtieri.maurizio@gmail.com. LA - eng PT - Journal Article DEP - 20140203 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (CXCL8 protein, human) RN - 0 (IL6 protein, human) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-6) RN - 0 (Interleukin-8) RN - 0 (Mutagens) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - 7OV03QG267 (Nickel) RN - C3574QBZ3Y (nickel monoxide) RN - EC 2.7.11.1 (ATM protein, human) RN - EC 2.7.11.1 (ATR protein, human) RN - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins) SB - IM MH - Alveolar Epithelial Cells/*drug effects/immunology/metabolism/pathology MH - Apoptosis/drug effects MH - Ataxia Telangiectasia Mutated Proteins/metabolism MH - Cell Cycle/drug effects MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - DNA Damage MH - Dose-Response Relationship, Drug MH - Endocytosis MH - Humans MH - Inflammation Mediators/*metabolism MH - Interleukin-6/metabolism MH - Interleukin-8/metabolism MH - MAP Kinase Signaling System/drug effects MH - Metal Nanoparticles/*toxicity MH - Mutagens/metabolism/*toxicity MH - NF-kappa B/metabolism MH - Necrosis MH - Nickel/metabolism/*toxicity MH - Phosphorylation MH - Reactive Oxygen Species/metabolism MH - Respiratory Mucosa/*drug effects/immunology/metabolism/pathology MH - Time Factors OTO - NOTNLM OT - Interleukins OT - MAP-kinases OT - NF-kB OT - Nickel oxide nanoparticles OT - Pulmonary epithelial cells OT - ROS EDAT- 2014/02/08 06:00 MHDA- 2014/05/03 06:00 CRDT- 2014/02/08 06:00 PHST- 2013/11/29 00:00 [received] PHST- 2014/01/24 00:00 [revised] PHST- 2014/01/27 00:00 [accepted] PHST- 2014/02/08 06:00 [entrez] PHST- 2014/02/08 06:00 [pubmed] PHST- 2014/05/03 06:00 [medline] AID - S0378-4274(14)00060-5 [pii] AID - 10.1016/j.toxlet.2014.01.040 [doi] PST - ppublish SO - Toxicol Lett. 2014 Apr 7;226(1):28-34. doi: 10.1016/j.toxlet.2014.01.040. Epub 2014 Feb 3.