title: Amorphous nanosilica induce endocytosis-dependent ROS generation and DNA damage in human keratinocytes.
abstract: BACKGROUND
  Clarifying the physicochemical properties of nanomaterials is crucial for hazard assessment and the safe application of these substances. With this in mind, we analyzed the relationship between particle size and the in vitro effect of amorphous nanosilica (nSP). Specifically, we evaluated the relationship between particle size of nSP and the in vitro biological effects using human keratinocyte cells (HaCaT).
  
  
  RESULTS
  Our results indicate that exposure to nSP of 70 nm diameter (nSP70) induced an elevated level of reactive oxygen species (ROS), leading to DNA damage. A markedly reduced response was observed using submicron-sized silica particles of 300 and 1000 nm diameter. In addition, cytochalasin D-treatment reduced nSP70-mediated ROS generation and DNA damage, suggesting that endocytosis is involved in nSP70-mediated cellular effects.
  
  
  CONCLUSIONS
  Thus, particle size affects amorphous silica-induced ROS generation and DNA damage of HaCaT cells. We believe clarification of the endocytosis pathway of nSP will provide useful information for hazard assessment as well as the design of safer forms of nSPs.
authors.affiliation: Osaka University, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nabeshi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Keigo
authors.initials: K
authors.lastname: Matsuyama
authors.forename: Yasutaro
authors.initials: Y
authors.lastname: Nakazato
authors.forename: Saeko
authors.initials: S
authors.lastname: Tochigi
authors.forename: Sayuri
authors.initials: S
authors.lastname: Kondoh
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hirai
authors.forename: Takanori
authors.initials: T
authors.lastname: Akase
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nagano
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Abe
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kamada
authors.forename: Norio
authors.initials: N
authors.lastname: Itoh
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsunoda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
mesh_terms: D002460:Cell Line; D020552:Comet Assay; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004359:Drug Therapy, Combination; D004705:Endocytosis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D053758:Nanoparticles / Q000633:toxicity*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D017382:Reactive Oxygen Species; D012822:Silicon Dioxide; D004247:DNA