期刊
ACS NANO
卷 11, 期 1, 页码 291-303出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.6b05652
关键词
carbon nanotubes; inhalation; aspiration; immune system; transcriptomics; inflammation; allergic airway inflammation
类别
资金
- Academy of Finland [139115, 275151, 292307]
- European Community's Seventh Framework Programme (FP7) [309329]
- Finnish Work Environment Fund [109137]
- Research Fundation of the University of Helsinki
- University of Eastern Finland
- Danish Centre for Nanosafety 2
- Academy of Finland (AKA) [139115, 139115] Funding Source: Academy of Finland (AKA)
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/m(3), 4 h/day for 4 days) or by oropharyngeal aspiration (10 or 40 mu g/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 mu g/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 mu g/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.
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