title: Toxicity of copper oxide nanoparticles in lung epithelial cells exposed at the air-liquid interface compared with in vivo assessment.
abstract: The toxicity of spark-generated copper oxide nanoparticles (CuONPs) was evaluated in human bronchial epithelial cells (HBEC) and lung adenocarcinoma cells (A549 cells) using an in vitro air-liquid interface (ALI) exposure system. Dose-response results were compared to in vivo inhalation and instillation studies of CuONPs. Cells were exposed to filtered, particle-free clean air (controls) or spark-generated CuONPs. The number median diameter, geometric standard deviation and total number concentration of CuONPs were 9.2 nm, 1.48 and 2.27×10(7)particles/cm(3), respectively. Outcome measures included cell viability, cytotoxicity, oxidative stress and proinflammatory chemokine production. Exposure to clean air (2 or 4h) did not induce toxicity in HBEC or A549 cells. Compared with controls, CuONP exposures significantly reduced cell viability, increased lactate dehydrogenase (LDH) release and elevated levels of reactive oxygen species (ROS) and IL-8 in a dose-dependent manner. A549 cells were significantly more susceptible to CuONP effects than HBEC. Antioxidant treatment reduced CuONP-induced cytotoxicity. When dose was expressed per area of exposed epithelium there was good agreement of toxicity measures with murine in vivo studies. This demonstrates that in vitro ALI studies can provide meaningful data on nanotoxicity of metal oxides.
authors.affiliation: Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242, USA. Electronic address: xuefang-jing@uiowa.edu.
authors.forename: Xuefang
authors.initials: X
authors.lastname: Jing
authors.affiliation: Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242, USA. Electronic address: jaehong-park@uiowa.edu.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242, USA. Electronic address: thomas-m-peters@uiowa.edu.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Peters
authors.affiliation: Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242, USA. Electronic address: peter-thorne@uiowa.edu.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Thorne
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D003300:Copper / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size
chemical_list: D000975:Antioxidants; D018925:Chemokines; D003300:Copper; C000520:cuprous oxide
keywords: Air–liquid interface; Copper oxide nanoparticles; Human bronchial epithelial cells; In vitro exposure; N-acetylcysteine; Oxidative stress