title: Toxicological Assessment of CoO and La2O3 Metal Oxide Nanoparticles in Human Small Airway Epithelial Cells.
abstract: Cobalt monoxide (CoO) and lanthanum oxide (La2O3) nanoparticles are 2 metal oxide nanoparticles with different redox potentials according to their semiconductor properties. By utilizing these two nanoparticles, this study sought to determine how metal oxide nanoparticle's mode of toxicological action is related to their physio-chemical properties in human small airway epithelial cells (SAEC). We investigated cellular toxicity, production of superoxide radicals and alterations in gene expression related to oxidative stress, and cellular death at 6 and 24 h following exposure to CoO and La2O3(administered doses: 0, 5, 25, and 50 µg/ml) nanoparticles. CoO nanoparticles induced gene expression related to oxidative stress at 6 h. After characterizing the nanoparticles, transmission electron microscope analysis showed SAEC engulfed CoO and La2O3nanoparticles. CoO nanoparticles were toxic after 6 and 24 h of exposure to 25.0 and 50.0 µg/ml administered doses, whereas, La2O3nanoparticles were toxic only after 24 h using the same administered doses. Based upon the Volumetric Centrifugation Methodin vivoSedimentation, Diffusion, and Dosimetry, the dose of CoO and La2O3nanoparticles delivered at 6 and 24 h were determined to be: CoO: 1.25, 6.25, and 12.5 µg/ml; La2O3: 5, 25, and 50 µg/ml and CoO: 4, 20, and 40 µg/ml; and La2O3: 5, 25, 50 µg/ml, respectively. CoO nanoparticles produced more superoxide radicals and caused greater stimulation of total tyrosine and threonine phosphorylation at both 6 and 24 h when compared with La2O3nanoparticles. Taken together, these data provide evidence that different toxicological modes of action were involved in CoO and La2O3metal oxide nanoparticle-induced cellular toxicity.
authors.affiliation: *Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505; yaq2@cdc.gov.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Sisler
authors.affiliation: *Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505;
authors.forename: Sandra V
authors.initials: SV
authors.lastname: Pirela
authors.affiliation: *Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505;
authors.forename: Justine
authors.initials: J
authors.lastname: Shaffer
authors.affiliation: *Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505;
authors.forename: Amy L
authors.initials: AL
authors.lastname: Mihalchik
authors.affiliation: *Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505;
authors.forename: William P
authors.initials: WP
authors.lastname: Chisholm
authors.affiliation: *Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505;
authors.forename: Michael E
authors.initials: ME
authors.lastname: Andrew
authors.affiliation: *Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505;
authors.forename: Diane
authors.initials: D
authors.lastname: Schwegler-Berry
authors.affiliation: Department of Pharmaceutical Sciences, West Virginia University, Morgantown, West Virginia 26505.
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.affiliation: T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts 02115; and.
authors.forename: Philip
authors.initials: P
authors.lastname: Demokritou
authors.affiliation: *Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505; yaq2@cdc.gov.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qian
mesh_terms: D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003035:Cobalt / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007811:Lanthanum / Q000737:chemistry / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D010087:Oxides / Q000737:chemistry / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects; D013499:Surface Properties
chemical_list: D010087:Oxides; D017382:Reactive Oxygen Species; D003035:Cobalt; C103829:lanthanum oxide; D007811:Lanthanum; C060728:cobalt oxide
keywords: cell culture; cytotoxicity; metal oxides; nanoparticles; oxidative stress.