DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology , Ljubljana , Slovenia.
Nanotoxicology (Impact Factor: 6.41). 11/2010; 5(3):341-53. DOI: 10.3109/17435390.2010.507316
Source: PubMed


We investigated the genotoxic responses to two types of TiO2 nanoparticles (<25 nm anatase: TiO(2)-An, and <100 nm rutile: TiO2-Ru) in human hepatoma HepG2 cells. Under the applied exposure conditions the particles were agglomerated or aggregated with the size of agglomerates and aggregates in the micrometer range, and were not cytotoxic. TiO2-An, but not TiO2-Ru, caused a persistent increase in DNA strand breaks (comet assay) and oxidized purines (Fpg-comet). TiO2-An was a stronger inducer of intracellular reactive oxygen species (ROS) than TiO2-Ru. Both types of TiO2 nanoparticles transiently upregulated mRNA expression of p53 and its downstream regulated DNA damage responsive genes (mdm2, gadd45α, p21), providing additional evidence that TiO2 nanoparticles are genotoxic. The observed differences in responses of HepG2 cells to exposure to anatase and rutile TiO2 nanoparticles support the evidence that the toxic potential of TiO2 nanoparticles varies not only with particle size but also with crystalline structure.

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    • "Concentration-dependent alterations in cell cycle progression have been observed in keratinocytes treated with TiO 2 -NPs (Huang et al., 2009; Kocbek et al., 2010). Also, TiO 2 NPs significantly alter the immune response, lipid and fatty acid metabolism, apoptosis in hepatocytes, and the activation of redox-sensitive signaling pathways (Petkovic et al., 2010; Singh et al., 2007; Thurn et al., 2007), all of which would implicate TiO 2 NPs in systemic health risks (Ferin and Leach, 1973; Horie et al., 2012; Kim et al., 2010; Lee et al., 1986; Singh et al., 2007). Many studies have highlighted that oxidative stress caused by metal oxides modulate several signaling pathways. "
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    • "Moreover, other in vitro studies have demonstrated that titanium dioxide (TiO 2 ) NMs can induce p53 expression by oxidative DNA damage. This p53 induction was associated with cell cycle arrest and apoptosis (Kang et al. 2008; Petkovic et al. 2011; Wu et al. 2010). The involvement of p53 was also implicated in the induction of apoptosis and carcinogenesis following the exposure of cNTs in rodent models (intraperitoneal injection and intratracheal instillation ) (Park et al. 2011; Poland et al. 2008; Takagi et al. 2008). "
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    • "Upon exposure, these released TiO 2 nanoparticles may interact with the human organism through inhalation or dermal contacts and get deposited inside the body. Various toxicological studies have demonstrated toxic effects of some types of TiO 2 nanoparticles in this case [13] [14] [15]. Few studies have examined the concentration, morphology and chemical composition of the generated aerosol wear particles [16] [17] [18]. "
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