Biomedical Engineering Reference
In-Depth Information
levels of proinflammatory cytokine and chemokine proteins, especially when the surface of the par-
ticles has been modified by silica to increase the hydrophilicity of the titanium dioxide-engineered
nanomaterial [65].
19.7.3.3 Genotoxicity of Engineered Nanomaterial
The number of studies exploring the genotoxic effect of engineered nanomaterial is small in view
of the large variety of different engineered nanomaterials already in the market. The methods are
being used for genotoxicity testing of engineered nanomaterials still inadequate for general conclu-
sions. Still, it is unclear how well standard genotoxicity tests designed for soluble chemicals can be
used to assess the genotoxicity of engineered nanomaterials. During the investigation, the possible
mechanism of engineered nanomaterial genotoxicity may be linked with the inflammatory process;
the question is whether
in vivo
tests are preferred over
in vitro
tests? It has been found that asbes-
tos fibers, such as the
Salmonella
mutagenicity test does not appear to be responsive to insoluble
engineered nanomaterial, probably because of the bacterial cell wall [80]. On the other hand, many
engineered nanomaterials appear to be positive in tests of DNA damage and micronuclei [81].
Exposure of mice to SWCNTs by intratracheal installation induced aortic mtDNA damage [82]
and DNA damage in bronchoalveolar lavage cells [83]. SWCNTs inhalation is more effective than
pharyngeal aspiration in causing K-ras gene mutations in mouse lungs at moderate doses [84], and
oral treatment of rats with SWCNT results in oxidative DNA adducts in the lungs and liver [85].
SWCNTs also increase DNA damage in Chinese hamster V79 lung fibroblasts and mouse embryo
fibroblasts and oxidative DNA damage in FE1-Muta
TM
mouse lung epithelial cells, but have no
significant effect on micronuclei in V79 cells or gene mutations in FE-1 cells [83,86]. As the doses
in the
in vivo
studies are relatively high, therefore, the assessment of their relevance for risk is prob-
lematic. The results of the
in vitro
studies are in many cases inconsistent, and carry the most likely
relevance to the risk assessment of these materials.
Xenopus laevis
larvae did not show induction of micronuclei in blood erythrocytes when grown
in the presence of double-walled CNTs [87]. A single intratracheal instillation of an MWCNT
increased the frequency of micronucleated type II pneumocytes in rat lungs
in vivo
in association
with a marked pulmonary inflammation [88].
In vitro
, MWCNTs induced micronuclei in the rat
lung epithelial RLE cells and human MCF-7 epithelial cells [88,89], DNA damage in RLE cells
[89], human lung epithelial A549 cells [90], and mesothelial cells [91], and a slight increase in gene
mutations in cultured mouse embryonic stem cells [92]. A mixture of SWCNTs and MWCNTs
induce a dose-dependent elevation of DNA damage and an increase in micronuclei
in vitro
in human
bronchial epithelial BEAS 2B cells [93].
In several research articles, the genotoxicity of nanosized TiO
2
has been described. However, due
to the use of different types of TiO
2
, various cell systems and variable assay conditions complicate
the comparison of the existing studies [94]. There is some indication that especially anatase phase
TiO
2
has genotoxic potential
in vitro
[94]. For example, the exposure of nanosized rutile (10 × 40 nm)
or nanosized anatase (<25 nm) into BEAS 2B cells for the duration of 0, 24, 48, or 72 h, provides the
evidence that in the comet assay, in both anatase and rutile dose-dependent effects were observed at
48 and 72 h. Micronuclei were only induced by nanosized rutile.
It indicates that more genotoxicity studies on engineered nanomaterial are immediately required,
and the need for novel methods to assess engineered nanomaterial-genome interactions. The geno-
toxicity potential of different engineered nanomaterials has been identified but the possible mecha-
nism is still unknown.
19.7.3.4 Carcinogenic Effects of Engineered Nanomaterial
The carcinogenic effects of asbestos may be due to the local generation of reactive oxygen and nitro-
gen species in association with emerging inflammation [95]. Studies with rats and mice have shown
that the MWCNT induces oxidative stress, inflammation, granulomas, and fibrosis in the lungs
[96]. The engineered nanomaterial with fibrogenic properties could induce cancers. Indeed, single
