Journal
NANOTOXICOLOGY
Volume 7, Issue 1, Pages 48-60Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/17435390.2011.629747
Keywords
Cellular uptake of TiO2 NPs; oxidative stress; genotoxicity; HepG2; apoptosis
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Funding
- CSIR, New Delhi [NWP35, OLP 009]
- Department of Science and Technology, Government of India [SR/S5/NM-01/2007]
- UK India Education and Research Initiative (UKIERI) [DST/INT/UKIERI/SA/P-10/2008]
- Department of Biotechnology, under the New INDIGO programme (NanoLINEN project)
- University Grant Commission (UGC), New Delhi
- ICMR-SRF fellowship
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Titanium dioxide nanoparticles (TiO2 NPs), widely used in consumer products, paints, pharmaceutical preparations and so on, have been shown to induce cytotoxicity, genotoxicity and carcinogenic responses in vitro and in vivo. The present study revealed that TiO2 NPs induce significant (p < 0.05) oxidative DNA damage by the Fpg-Comet assay even at 1 mu g/ml concentration. A corresponding increase in the micronucleus frequency was also observed. This could be attributed to the reduced glutathione levels with concomitant increase in lipid peroxidation and reactive oxygen species generation. Furthermore, immunoblot analysis revealed an increased expression of p53, BAX, Cyto-c, Apaf-1, caspase-9 and caspase-3 and decreased the level of Bcl-2 thereby indicating that apoptosis induced by TiO2 NPs occurs via the caspase-dependent pathway. This study systematically shows that TiO2 NPs induce DNA damage and cause apoptosis in HepG2 cells even at very low concentrations. Hence the use of such nanoparticles should be carefully monitored.
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