title: Repetitive exposure to zinc oxide nanoparticles induces dna damage in human nasal mucosa mini organ cultures.
abstract: Data on the toxicological properties of zinc oxide nanoparticles (ZnO-NPs) is incomplete. ZnO-NPs may enter humans via inhalation or ingestion. The aim of the current study was to evaluate ZnO-NP-induced genotoxicity in three-dimensional (3D) mini organ cultures (MOCs) of human nasal mucosa following repeated exposure to ZnO-NP and regeneration. Nasal MOCs of 10 patients and ZnO-NPs were cultivated for one week and then characterized by electron microscopy. Nasal MOCs were partially covered by ciliated epithelium after one week of cultivation. ZnO-NPs were distributed to the cytoplasm and the nucleus. MOCs were exposed once, twice, or three times to 0.1 or 5 μg/ml of ZnO-NPs for 1 hr per exposure and were then evaluated for cytotoxicity and genotoxicity. MOCs were cultivated for 24 hr after the triple ZnO-NP exposure to allow for regeneration. ZnO-NP exposure did not result in significant cytotoxicity or apoptosis, as determined by trypan blue exclusion and caspase-3 activity, respectively. A significant increase in DNA damage was detected following repetitive exposure compared to single exposure to ZnO-NPs at 5 μg/ml, but not 0.1 μg/ml ZnO-NPs. At both concentrations of ZnO-NP, DNA fragmentation increased after 24 hr of regeneration. In contrast, DNA damage which was induced by the positive control, methyl methanesulfonate, was significantly reduced after 24-hr regeneration. Thus, our results suggest that repetitive exposure to low concentrations of ZnO-NPs results in persistent or ongoing DNA damage.
authors.affiliation: Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University of Wuerzburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hackenberg
authors.forename: Franz-Zeno
authors.initials: FZ
authors.lastname: Zimmermann
authors.forename: Agmal
authors.initials: A
authors.lastname: Scherzed
authors.forename: Gudrun
authors.initials: G
authors.lastname: Friehs
authors.forename: Katrin
authors.initials: K
authors.lastname: Froelich
authors.forename: Christian
authors.initials: C
authors.lastname: Ginzkey
authors.forename: Christian
authors.initials: C
authors.lastname: Koehler
authors.forename: Marc
authors.initials: M
authors.lastname: Burghartz
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hagen
authors.forename: Norbert
authors.initials: N
authors.lastname: Kleinsasser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D053758:Nanoparticles / Q000633:toxicity*; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D017382:Reactive Oxygen Species / Q000378:metabolism; D055815:Young Adult; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D015034:Zinc Oxide