Toxicological Effects of Metal Oxide Nanomaterials - Safety of Nanomaterials along Their Lifecycle - page 161

TABLE 8.1
Origin of the Cell Lines Used within the nanoGEM Project

Catalogue
Number Cell Line Species Origin Provider

A549 Homo Sapiens Lung adenocarcinoma, alveolar

epithelium-like

ATCC CCL-185

HaCaT H. sapiens Skin, keratinocytes CLS -

MDCK (NBL-2) Canis familiaris Kidney, epithelium-like ATCC CCL-34

NIH-3T3 Mus musculus Embryo, fibroblasts DSMZ ACC 59

NRK-52E Rattus norvegicus Kidney, epithelium-like DSMZ ACC 199

RAW 264.7 R. norvegicus Macrophages, AML virus

transformed

ATCC TIB-71

RLE-6TN R. norvegicus Lung, alveolar epithelium-like ATCC CRL-2300

properties that drive the metal oxide nanoparticles' cytotoxicity with emphasis on
the results obtained by these two projects as well as from other studies that have been
conducted using well-characterized nanomaterials and multiple test systems. The
effects of metal oxide nanoparticles and the physicochemical properties identified to
be responsible for these effects are summarized in Table 8.2.

8.2.1 o xidative s tress
Recent evidence suggests that oxidative stress initiated by the formation of ROS is
a key route, thereby inducing cell damage. The ROS generating capacity of metal
oxide nanoparticles seems to correlate with their ability to induce cellular inflamma-
tion and DNA damage (Xu et al. 2009; Sayes et al. 2006; Sayes, Reed, and Warheit
2007).
The exposure of BEAS-2B cells to ZnO nanoparticles, for example, led to an
increase in intracellular ROS levels and decreased cell viability over time and this
cytotoxic effect was reduced by N -acetyl cysteine treatment (Huang et al. 2010). This
suggests that oxidative stress is closely related to the cytotoxicity of nanoparticles.
Thus, measuring the oxidative stress potential of metal oxide nanoparticles becomes
mandatory in the nanoparticle toxicity assessment.
To determine the impact of the chemical composition/identity and its catalytic
activity on ROS formation, Limbach et al. (2007) exposed human lung epithelial
cells (A549) to thoroughly characterized particles of similar morphology, com-
parable size, shape, and degree of agglomeration. Their studies suggest that the
chemical composition of nanoparticles is a decisive factor influencing ROS forma-
tion in lung epithelial cells (Limbach et al. 2007). This could be further confirmed
by a study comparing mixed metal oxide nanoparticles of titanium dioxide and
zirconium dioxide (TiO 2 -ZrO 2 ). The nanoparticle mixtures containing the largest
amount of TiO 2 (90%) induced ROS formation in seven of ten cell lines tested,
whereas Ti-Zr mixed nanoparticles with lower amounts of TiO 2 (10%, 50%) did
not lead to an increase in ROS production in any of the cell lines tested (Kroll
et al. 2011). The induction of oxidative stress was also evaluated in primary mouse