Biomedical Engineering Reference
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fiber shape of CNTs is similar to asbestos fibers. The asbestos-like, length-dependent, pathogenic
behaviors of CNTs induce pulmonary toxicity (Craig et  al., 2008). Depending upon the size and
physical structure of nanosized particles, they are deposited in different regions of the respiratory
tract (Oberdorster et  al., 2005) and cause pulmonary toxicity. These include pulmonary inflam-
mation, pulmonary fibrosis, the induced accumulation of neutrophils and eosinophils, mechani-
cal blockages, and increases in various cytotoxicity/inflammatory markers (bronchoalveolar lavage
cells, polymorphonuclear leukocytes lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-
α), interleukin-1β (IL-1β), and mucin) in the lungs (Muller et al., 2005, Han et al., 2008).
6.4 PULMONARY TOXICITY OF SWCNTs
SWCNTs can be about 1-4 nm in diameter and several hundred nanometers in length, making
them structurally similar to the thread-like filaments of pulmonary basement membranes (type
IV collagen) (Shvedova et al., 2005, Kuhn, 1995). SWCNTs are quickly incorporated into the pul-
monary interstitial space with rare incorporations by alveolar macrophages; SWCNTs were com-
monly found in submicron groups and were rarely found as a single structure (Mercer et al., 2008).
Table 6.2 shows the major toxicities caused by SWCNTs in animals and human. Cytotoxicity in
human alveolar carcinoma epithelial cells (Casey et al., 2008) and oxidative stress in mouse lung
epithelial cells (Jacobsen et al., 2008) can be caused by SWCNT exposure. The aspiration or inhala-
tion of SWCNTs in mice caused a rapid granulomatous response and progressive interstitial fibro-
sis (Shvedova et al., 2008a). In addition, SWCNTs caused a greater increase of connective tissue
thickness to the alveolar interstitial space of mice when compared with MWCNTs, suggesting that
SWCNTs are more fibrogenic in mice lungs (Mercer et al., 2011). CNT-induced fibrosis is thought
to be caused by fibroblast proliferation, collagen production, and elevations of matrix metallopro-
teinase-9 as demonstrated in human lung fibroblast cell cultures treated with SWCNTs (Wang et al.,
2010). CNTs are able to induce an allergic immune response in mice using a subcutaneous injec-
tion and intranasal models (Nygaard et al., 2009). The pharyngeal aspiration of SWCNTs in mice
significantly decreased the clearance of Listeria monocytogenes exposure from the lungs of the
mice. In addition, the SWCNT-treated mice had a decreased lung macrophage phagocytic activ-
ity as well as less nitric oxide production. This suggests that SWCNT-treated mice are more prone
to pulmonary infections (Shvedova et  al., 2008b). A mouse lung epithelial cell line exposed to
SWCNTs was positive for a Comet assay (single-cell gel elecrophoresis), which measures genotoxic-
ity, that is, DNA damage, as measured by strand breaks or formamidopyrimidine DNA glycosylase
sites (Jacobsen et  al., 2008). Chinese hamster lung fibroblast cell cultures exposed to SWCNTs
were positive for genotoxicity in the Comet assay and micronucleus test (Kisin et al., 2011). Single
intragastric administrations of SWCNT to rats caused genotoxicity in their liver and lungs as mea-
sured by the formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine, which is a measure of oxidatively
TABLE 6.2
Pulmonary Toxicity of SWCNTs
Species
Toxicity
References
Human
Lung cytotoxicity
Casey et al. (2008)
Mouse
Lung epithelial cells oxidative stress and genotoxicity
Jacobsen et al. (2008)
Mouse
Lung interstitial fibrosis and K-ras gene mutations
Shvedova et al. (2008a)
Mouse
Lung fibrosis
Mercer et al. (2011)
Human
Lung cell culture fibrosis
Wang et al. (2010)
Mouse
Intranasal immune response
Nygaard et al. (2009)
Mouse
Decreased clearance of lung bacteria
Shvedova et al. (2008b)
Hamster
Genotoxicity of lung fibroblast cells
Kisin et al. (2011)
 
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