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Toxicological Impacts of Nanomaterials 403

primary human umbilical vein endothelial cells in culture exposed to
carbon nanotubes showed no toxicity based on cell viability and cell
metabolic activity (Flahaut et al., 2006).
Carbon nanotubes carrying DNA or peptide molecules can serve as a
potential delivery system in gene or peptide delivery (Gao et al., 2003).
Other investigators studied the effect of SWCNT with the idea that they
are biocompatible. These investigators have shown that SWCNT can
inhibit cell proliferation and decrease cell adhesive ability in a dose- and
time-dependent fashion using human embryo kidney HEK293 cells (Cui
et al., 2005). Exogenous DNA can be introduced into mammalian cells
by manipulating signal transduction by nanospearing, which is based on
penetrating nickel embedded nanotubes into the cell membranes by
magnetic fields (Cai et al., 2005). Mouse peritoneal macrophage-like
cells can ingest SWCNT in a surfactant without changes in viability or
population growth (Cherukuri et al., 2004). Iron-rich SWCNT have been
shown to cause a significant loss of intracellular thiols and accumulation
of lipid peroxides in macrophages (Kagan et al., 2006). Studies have also
shown activation of oxidative stress and nuclear transcription factor-kB
in immortalized keratinocytes (Manna et al., 2005). Nucleic acid encap-
sulated SWCNT have been located within cytoplasmic vacuoles of
myoblast stem cells and have been shown to be persistent with Raman
scattering and fluorescence spectra in mammalian cells for up to three
months in culture, which makes these DNA-SWCNT function as long-
term cellular biomarkers or sensors (Heller et al., 2005).

Multi-Walled Carbon Nanotubes (MWCNT)
MWCNT toxicity has also been addressed in a primary human ker-
atinocyte cell culture model. Human neonatal epidermal keratinocytes
exposed to 0.1, 0.2, and 0.4 mg/ml of MWCNT for 1, 2, 4, 8, 12, 24, and
48 hours depicted MWCNT within the cytoplasmic vacuoles of human
epidermal keratinocytes. These MWCNT exhibited typical base mode
growth; very little disordered carbon, and were well ordered and aligned.
Using transmission electron microscopy, MWCNT were predominantly
located in vacuoles in the cytoplasm of the keratinocyte and were found
up to 3.6 µ in length (Figure 11.3). At 24 hours, 59 percent of the human
keratinocytes contained MWCNT, compared to 84 percent by 48 hours
at the 0.4 mg/ml dose. The viability of these cells decreased with an
increase in MWCNT concentration. IL-8, an early biomarker for
irritation, increased with time and concentration (Monteiro-Riviere
et al., 2005a). Proteomic analysis conducted in human epidermal
keratinocytes exposed to MWCNT showed altered expression of
36 proteins after 24 hours and 106 altered proteins after 48 hours rel-
ative to controls. These protein alterations suggested dysregulation of