title: Intracellular accumulation of indium ions released from nanoparticles induces oxidative stress, proinflammatory response and DNA damage.
abstract: Due to the widespread use of indium tin oxide (ITO), it is important to investigate its effect on human health. In this study, we evaluated the cellular effects of ITO nanoparticles (NPs), indium chloride (InCl3) and tin chloride (SnCl3) using human lung epithelial A549 cells. Transmission electron microscopy and inductively coupled plasma mass spectrometry were employed to study cellular ITO NP uptake. Interestingly, greater uptake of ITO NPs was observed, as compared with soluble salts. ITO NP species released could be divided into two types: 'indium release ITO' or 'tin release ITO'. We incubated A549 cells with indium release ITO, tin release ITO, InCl3 or SnCl2 and investigated oxidative stress, proinflammatory response, cytotoxicity and DNA damage. We found that intracellular reactive oxygen species were increased in cells incubated with indium release ITO, but not tin release ITO, InCl3 or SnCl2. Messenger RNA and protein levels of the inflammatory marker, interleukin-8, also increased following exposure to indium release ITO. Furthermore, the alkaline comet assay revealed that intracellular accumulation of indium ions induced DNA damage. Our results demonstrate that the accumulation of ionic indium, but not ionic tin, from ITO NPs in the intracellular matrix has extensive cellular effects.
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology, 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan y-tabei@aist.go.jp.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tabei
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology, 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan.
authors.forename: Akinari
authors.initials: A
authors.lastname: Sonoda
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology, 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nakajima
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology, 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan.
authors.forename: Vasudevanpillai
authors.initials: V
authors.lastname: Biju
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology, 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Makita
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology, 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology, 2217-14 Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Horie
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D006801:Humans; D007204:Indium / Q000737:chemistry / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced*; D016209:Interleukin-8 / Q000378:metabolism; D007477:Ions / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D017971:Tin Compounds / Q000737:chemistry / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D007477:Ions; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D017971:Tin Compounds; D007204:Indium; C023599:stannous chloride; C020758:indium trichloride; C109984:indium tin oxide
keywords: DNA damage; indium tin oxide; nanoparticles; oxidative stress; proinflammatory response