Uptake and Effects of Carbon Nanotubes - Safety of Nanomaterials along Their Lifecycle - page 222

size and geometry of SWCNT bundles might account for physical interaction of
SWCNT with the microtubules that form the mitotic spindle. Zhu et al assessed
the DNA damage response to MWCNTs in mouse embryonic stem (ES) cells and
found that MWCNTs can accumulate and induce apoptosis in mouse ES cells and
activate the tumor suppressor protein p53, a marker of DNA damage (Zhu et al.
2007). Finally, Patlolla et al. showed that MWCNTs caused dose-dependent geno-
toxic effects of structural chromosome aberrations, DNA damage, and micronuclei
formulation in mice when administered by intraperitoneal injection (Patlolla et al.
2010). Recently, persistent DNA damage was reported in rat lung cells after five
days of inhalation exposure and one month postexposure to dispersed MWCNTs
(Kim et al. 2012). Collectively, these studies show that SWCNTs and MWCNTs
have genotoxic effects in cultured cells and can reach sensitive sites in vivo to cause
genotoxic effects.
10.4.3 e ffeCts of Cnt s Beyond l ungs
Inhaled CNTs can stimulate the immune system beyond the boundaries of the
lung to impact distant organ systems, including the spleen and heart. Mitchell and
coworkers showed that inhaled MWCNTs cause systemic immunosuppression and
splenic oxidative stress (Mitchell 2007). The mechanism of splenic immunosuppres-
sion was further elucidated and involves the release of TGF-β1 from the lungs of
MWCNT-exposed mice, which enters the bloodstream to signal COX-2-mediated
increases in prostaglandin-E2 and IL-10 in the spleen, both of which play a role in
suppressing T cell proliferation (Mitchell 2009). Erdely and coworkers also reported
that SWCNTs or MWCNTs deposited into the lungs induced acute lung and systemic
effects, suggesting that the systemic response, if chronic and persistent, could trig-
ger or exacerbate cardiovascular dysfunction and disease (Erdely et al. 2009).
Collectively, these studies suggest that inhaled CNTs could have profound effects
on systemic targets.
10.4.4 s usCePtiBility f aCtors
Careful consideration should be given to the possibility that CNTs might have the
most profound adverse health effects on individuals with pre-existing respiratory dis-
eases such as asthma, bronchitis, or chronic obstructive pulmonary disease (COPD)
(Bonner 2010a; Bonner 2011). Some susceptibility factors that might determine CNT
toxicity are illustrated in Figure 10.6. MWCNTs have been shown to exacerbate
pre-existing allergic airway diseases in mice that were first prechallenged with oval-
bumin allergen (Ryman-Rasmussen et al. 2009b; Inoue et al. 2009). These studies
suggest that CNTs pose a hazard to individuals with allergic asthma. SWCNTs have
also been reported to exacerbate allergic airway inflammation in mice via enhanced
activation of Th immunity and increased oxidative stress (Inoue et al. 2010; Nygaard
et al. 2009). Repeated exposure to MWCNTs has also been shown to induce Th2
allergic responses in the absence of any allergen pre-exposure (Park et al. 2009).
Although these studies suggest that individuals with allergic asthma are susceptible
to lung and airway diseases caused by CNTs exposure, it remains unknown whether