Biomedical Engineering Reference
In-Depth Information
Nanoparticles in general are known to increase in the oxidative stress by the virtue of enhancing
the production of ROS within cells [148]. Since fullerenes, by the virtue of their size, belong to a sub-
category of nanoparticles, it is important to understand their effects in this context. Sayes et al. [149],
using a variety of cell lines, such as dermal fibroblasts, hepatocytes, and astrocytes, demonstrated
cytotoxicity of
nano
C
60
mediated via increased ROS production. The ROS-mediated mechanism of
toxicity was ascertained by the protective effects observed upon the administration of an antioxidant,
that is, ascorbic acid, against fullerene-induced cytotoxicity. Similarly, Kamat et al. [150] observed
the oxidative toxicities of fullerenes (C
60
) and polyhydroxylated fullerenes (C
60
)OH
22-26
, within iso-
lated rat liver microsomes. The production of oxidized metabolites, along with blockage of toxic
effects by antioxidants, confirmed the oxidative mechanism of toxicity. In a contradictory study, Xia
et al. [151] demonstrated that polyhydroxy derivatives of fullerenes failed to produce an oxidative
response as measured by ROS production, glutathione depletion, or heme oxygenase 1 stimulation in
macrophages, although mitochondrial damage was observed. In the same study, the authors evalu-
ated a variety of nanoparticles and found that there was a significant difference in the abilities of
these particles to increase oxidative stress and the magnitude of induced toxicity.
Several researchers have utilized standard genotoxicity tests and assays to evaluate the potential
mutagenic effects of fullerenes on DNA. The commonly used tests for genotoxicity include the
Ames test, comet assay, and the influence on tumor formation in biological systems.
Using a comet assay, Dhawan et al. [152] evaluated the DNA damaging potential of C
60
within
human lymphocytes. The authors demonstrated that fullerene particles prepared using differ-
ent dispersion solvents, that is water or ethanol, showed a genotoxic response within cells, with a
higher degree of toxicity elicited by fullerenes dispersed in water. In a different study, Sera et al.
[153] investigated the influence of light and dark conditions on the mutagenic effects of fuller-
enes using the Ames test. The authors observed that fullerenes produced mutagenic effects on
Salmonella typhimurium
DNA in the presence of light via the production of ROS. DNA damage
due to oxidative processes was demonstrated by increases in lipid peroxidation and the formation
of 8-hydroxydeoxyguanosine.
9.3.2 h
ealth
e
ffects
of
c
arBoN
N
aNotuBes
The similarities in physical properties between CNTs and asbestos have led to questions regarding
the biological safety of CNT exposure [154]. Indeed, studies of single-walled CNT (SWCNT) and
multiwalled CNT (MWCNT) in biological systems—both
in vitro
and
in vivo
—have resulted in
DNA strand breakages and oxidative damages, chromosomal damages and mutations, and tissue
inflammatory responses among other biological responses [154,155]. Besides being able to induce
DNA breakages in a variety of
in vitro
models, SWCNTs and MWCNTs also showed similar effects
in
in vivo
models [154]. CNTs induced the most breakage in DNA strands when investigating the
effect of nano-sized biomaterials in fibroblasts [156]. This was validated by another study that
showed purified functionalized MWCNTs induced greater DNA strand damage than nonfunction-
alized MWCNTs, demonstrating stronger genotoxic potential [157]. Furthermore, pulmonary and
hepatic production of 8-oxo-2′-deoxyguanosine (8-OHdG), an indicator of DNA oxidation, was
detected in rats given SWCNTs (0.064 and 0.64 mg/kg) orally [158]. Significant DNA damage was
also exhibited in lung and tracheal tissues, through inhalation exposure and injection of CNTs,
respectively, among various other
in vivo
toxicology studies [154,159-161].
The genotoxic potential in CNTs may also contribute to chromosomal changes in biological
systems, possibly as a result of structural defects in the CNTs [162]. CNTs were shown to disturb
mitotic spindle formation, which could contribute to chromosomal changes and aneuploidy, along
with multinucleation, in
in vitro
and
in vivo
biological systems exposed to CNTs [154,163], possibly
a result of the CNTs' physical similarity to cellular microtubules [164]. Indeed, Sargent et al. [165]
observed the presence and interaction of SWCNTs with centrosomes and mitotic spindles inside
