TiO2 nanoparticles induce oxidative DNA damage and apoptosis in human liver cells

Ritesh K. Shukla, Ashutosh Kumar, Deepak Gurbani, Alok K. Pandey, Shashi Singh, Alok Dhawan

Research output: Contribution to journalArticlepeer-review

200 Scopus citations


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 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.

Original languageEnglish (US)
Pages (from-to)48-60
Number of pages13
Issue number1
StatePublished - Feb 2013
Externally publishedYes


  • Apoptosis
  • Cellular uptake of TiO2 NPs
  • HepG2
  • Oxidative stress; genotoxicity

ASJC Scopus subject areas

  • Biomedical Engineering
  • Toxicology


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