title: Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells.
abstract: BACKGROUND
  Single-wall carbon nanotubes (SWCNTs), with their unique physicochemical and mechanical properties, have many potential new applications in medicine and industry. There has been great concern subsequent to preliminary investigations of the toxicity, biopersistence, pathogenicity, and ability of SWCNTs to translocate to subpleural areas. These results compel studies of potential interactions of SWCNTs with mesothelial cells.
  
  
  OBJECTIVE
  Exposure to asbestos is the primary cause of malignant mesothelioma in 80-90% of individuals who develop the disease. Because the mesothelial cells are the primary target cells of asbestos-induced molecular changes mediated through an oxidant-linked mechanism, we used normal mesothelial and malignant mesothelial cells to investigate alterations in molecular signaling in response to a commercially manufactured SWCNT.
  
  
  METHODS
  In the present study, we exposed mesothelial cells to SWCNTs and investigated reactive oxygen species (ROS) generation, cell viability, DNA damage, histone H2AX phosphorylation, activation of poly(ADP-ribose) polymerase 1 (PARP-1), stimulation of extracellular signal-regulated kinase (ERKs), Jun N-terminal kinases (JNKs), protein p38, and activation of activator protein-1 (AP-1), nuclear factor kappaB (NF-kappaB), and protein serine-threonine kinase (Akt).
  
  
  RESULTS
  Exposure to SWCNTs induced ROS generation, increased cell death, enhanced DNA damage and H2AX phosphorylation, and activated PARP, AP-1, NF-kappaB, p38, and Akt in a dose-dependent manner. These events recapitulate some of the key molecular events involved in mesothelioma development associated with asbestos exposure.
  
  
  CONCLUSIONS
  The cellular and molecular findings reported here do suggest that SWCNTs can cause potentially adverse cellular responses in mesothelial cells through activation of molecular signaling associated with oxidative stress, which is of sufficient significance to warrant in vivo animal exposure studies.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA.
authors.forename: Maricica
authors.initials: M
authors.lastname: Pacurari
authors.forename: Xuejun J
authors.initials: XJ
authors.lastname: Yin
authors.forename: Jinshun
authors.initials: J
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Ding
authors.forename: Steve S
authors.initials: SS
authors.lastname: Leonard
authors.forename: Diane
authors.initials: D
authors.lastname: Schwegler-Berry
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Ducatman
authors.forename: Deborah
authors.initials: D
authors.lastname: Sbarra
authors.forename: Mark D
authors.initials: MD
authors.lastname: Hoover
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.forename: Val
authors.initials: V
authors.lastname: Vallyathan
mesh_terms: D015153:Blotting, Western; D020552:Comet Assay; D004249:DNA Damage; D004789:Enzyme Activation; D006657:Histones / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D037742:Nanotubes, Carbon; D018301:Neoplasms, Mesothelial / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D006657:Histones; D016328:NF-kappa B; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
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