title: Effects of Fe3O4 Magnetic Nanoparticles on A549 Cells.
abstract: Fe3O4 magnetic nanoparticles (MgNPs-Fe3O4) are widely used in medical applications, including magnetic resonance imaging, drug delivery, and in hyperthermia. However, the same properties that aid their utility in the clinic may potentially induce toxicity. Therefore, the purpose of this study was to investigate the cytotoxicity and genotoxicity of MgNPs-Fe3O4 in A549 human lung epithelial cells. MgNPs-Fe3O4 caused cell membrane damage, as assessed by the release of lactate dehydrogenase (LDH), only at a high concentration (100 μg/mL); a lower concentration (10 μg/mL) increased the production of reactive oxygen species, increased oxidative damage to DNA, and decreased the level of reduced glutathione. MgNPs-Fe3O4 caused a dose-dependent increase in the CD44+ fraction of A549 cells. MgNPs-Fe3O4 induced the expression of heme oxygenase-1 at a concentration of 1 μg/mL, and in a dose-dependent manner. Despite these effects, MgNPs-Fe3O4 had minimal effect on cell viability and elicited only a small increase in the number of cells undergoing apoptosis. Together, these data suggest that MgNPs-Fe3O4 exert little or no cytotoxicity until a high exposure level (100 μg/mL) is reached. This dissociation between elevated indices of cell damage and a small effect on cell viability warrants further study.
authors.affiliation: Laboratory for Medical Engineering, Division of Materials and Chemical Engineering, Graduate School of Engineering, Yokohama National University, Yokohama 240-8501, Japan. mawata@ynu.ac.jp
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Misao
authors.initials: M
authors.lastname: Yoneda
authors.forename: Ayaka
authors.initials: A
authors.lastname: Morohashi
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Hori
authors.forename: Daiki
authors.initials: D
authors.lastname: Okamoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Sato
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kurioka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nittami
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Hirokawa
authors.forename: Taizo
authors.initials: T
authors.lastname: Shiraishi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kawai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kasai
authors.forename: Yukari
authors.initials: Y
authors.lastname: Totsuka
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005290:Ferric Compounds / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000633:toxicity*; D009152:Mutagenicity Tests; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D018960:Hyaluronan Receptors; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; C000499:ferric oxide; D007770:L-Lactate Dehydrogenase; D051547:Heme Oxygenase-1; D005978:Glutathione
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