title: Inhalation and Oropharyngeal Aspiration Exposure to Rod-Like Carbon Nanotubes Induce Similar Airway Inflammation and Biological Responses in Mouse Lungs.
abstract: Carbon nanotubes (CNTs) have the potential to impact technological and industrial progress, but their production and use may, in some cases, cause serious health problems. Certain rod-shaped multiwalled CNTs (rCNTs) can, in fact, induce severe asbestos-like pathogenicity in mice, including granuloma formation, fibrosis, and even cancer. Evaluating the comparability between alternative hazard assessment methods is needed to ensure fast and reliable evaluation of the potentially adverse effects of these materials. To compare two alternative airway exposure methods, C57BL/6 mice were exposed to rCNTs by a state-of-the-art but laborious and expensive inhalation method (6.2-8.2 mg/m3, 4 h/day for 4 days) or by oropharyngeal aspiration (10 or 40 μg/day for 4 days), which is cheaper and easier to perform. In addition to histological and cytological studies, transcriptome analysis was also carried out on the lung tissue samples. Both inhalation and low-dose (10 μg/day) aspiration exposure to rCNTs promoted strong accumulation of eosinophils in the lungs and recruited also a few neutrophils and lymphocytes. In contrast, the aspiration of a high-dose (40 μg/day) rCNT caused only a mild pulmonary eosinophilia but enhanced accumulation of neutrophils in the airways. Inhalation and low-dose aspiration exposure promoted comparable giant cell formation, mucus production, and IL-13 expression in the lungs. Both exposure methods also exacerbated similar expression alterations with 154 (56.4%) differentially expressed, overlapping genes in microarray analyses. Of all differentially expressed genes, up to 80% of the activated biological functions were shared according to pathway enrichment analyses. Inhalation and low-dose aspiration elicited very similar pulmonary inflammation providing evidence that oropharyngeal aspiration is a valid approach and a convenient alternative to the inhalation exposure for the hazard assessment of nanomaterials.
authors.forename: Pia
authors.initials: P
authors.lastname: Kinaret
authors.forename: Marit
authors.initials: M
authors.lastname: Ilves
authors.forename: Vittorio
authors.initials: V
authors.lastname: Fortino
authors.affiliation: Finnish Institute of Occupational Health , Helsinki 00251, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Rydman
authors.forename: Piia
authors.initials: P
authors.lastname: Karisola
authors.affiliation: Fine Particle and Aerosol Technology Laboratory, Department of Environmental and Biological Sciences, University of Eastern Finland , Kuopio 80100, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Lähde
authors.affiliation: National Research Centre for the Working Environment , Copenhagen DK-2100, Denmark.
authors.forename: Joonas
authors.initials: J
authors.lastname: Koivisto
authors.affiliation: Fine Particle and Aerosol Technology Laboratory, Department of Environmental and Biological Sciences, University of Eastern Finland , Kuopio 80100, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Jokiniemi
authors.affiliation: Finnish Institute of Occupational Health , Helsinki 00251, Finland.
authors.forename: Henrik
authors.initials: H
authors.lastname: Wolff
authors.affiliation: Finnish Institute of Occupational Health , Helsinki 00251, Finland.
authors.forename: Kai
authors.initials: K
authors.lastname: Savolainen
authors.forename: Dario
authors.identifier: 0000-0001-9195-9003
authors.initials: D
authors.lastname: Greco
authors.affiliation: Institute of Environmental Medicine (IMM), Karolinska Institutet , Stockholm 171 77, Sweden.
authors.forename: Harri
authors.identifier: 0000-0003-0106-8923
authors.initials: H
authors.lastname: Alenius
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D005260:Female; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D037742:Nanotubes, Carbon / Q000737:chemistry*; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism
chemical_list: D037742:Nanotubes, Carbon
keywords: allergic airway inflammation; aspiration; carbon nanotubes; immune system; inflammation; inhalation; transcriptomics