title: Surface modification does not influence the genotoxic and inflammatory effects of TiO2 nanoparticles after pulmonary exposure by instillation in mice.
abstract: The influence of surface charge of nanomaterials on toxicological effects is not yet fully understood. We investigated the inflammatory response, the acute phase response and the genotoxic effect of two different titanium dioxide nanoparticles (TiO2NPs) following a single intratracheal instillation. NRCWE-001 was unmodified rutile TiO2with endogenous negative surface charge, whereas NRCWE-002 was surface modified to be positively charged. C57BL/6J BomTac mice received 18, 54 and 162 µg/mouse and were humanely killed 1, 3 and 28 days post-exposure. Vehicle controls were tested alongside for comparison. The cellular composition and protein concentration were determined in bronchoalveolar lavage (BAL) fluid as markers for an inflammatory response. Pulmonary and systemic genotoxicity was analysed by the alkaline comet assay as DNA strand breaks in BAL cells, lung and liver tissue. The pulmonary and hepatic acute phase response was analysed by Saa3 mRNA levels in lung tissue or Saa1 mRNA levels in liver tissue by real-time quantitative polymerase chain reaction. Instillation of NRCWE-001 and -002 both induced a dose-dependent neutrophil influx into the lung lining fluid and Saa3 mRNA levels in lung tissue at all assessed time points. There was no statistically significant difference between NRCWE-001 and NRCWE-002. Exposure to both TiO2NPs induced increased levels of DNA strand breaks in lung tissue at all doses 1 and 28 days post-exposure and NRCWE-002 at the low and middle dose 3 days post-exposure. The DNA strand break levels were statistically significantly different for NRCWE-001 and -002 for liver and for BAL cells, but no consistent pattern was observed. In conclusion, functionalisation of reactive negatively charged rutile TiO2to positively charged did not consistently influence pulmonary toxicity of the studied TiO2NPs.
authors.affiliation: National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark.|Institute of Public Health, University of Copenhagen, DK-1353 Copenhagen K, Denmark and.
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.affiliation: National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Zdenka O
authors.initials: ZO
authors.lastname: Kyjovska
authors.affiliation: National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Poulsen
authors.affiliation: National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Nicklas R
authors.initials: NR
authors.lastname: Jacobsen
authors.affiliation: National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Anne T
authors.initials: AT
authors.lastname: Saber
authors.affiliation: National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bengtson
authors.affiliation: National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Petra
authors.initials: P
authors.lastname: Jackson
authors.affiliation: National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark, ubv@nrcwe.dk.|Department of Micro- and Nanotechnology, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
mesh_terms: D000210:Acute-Phase Reaction; D000818:Animals; D020552:Comet Assay; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D014025:Titanium / Q000494:pharmacology / Q000633:toxicity*
chemical_list: C009495:titanium dioxide; D004247:DNA; D014025:Titanium