, Volume 17, Issue 8, pp 852–870 | Cite as

Zinc oxide nanoparticles induce oxidative DNA damage and ROS-triggered mitochondria mediated apoptosis in human liver cells (HepG2)

  • Vyom Sharma
  • Diana Anderson
  • Alok DhawanEmail author
Original Paper


The wide scale use of Zinc oxide (ZnO) nanoparticles in the world consumer market makes human beings more prone to the exposure to ZnO nanoparticles and its adverse effects. The liver, which is the primary organ of metabolism, might act as a major target organ for ZnO nanoparticles after they gain entry into the body through any of the possible routes. Therefore, the aim of the present study was to assess the apoptotic and genotoxic potential of ZnO nanoparticles in human liver cells (HepG2) and the underlying molecular mechanism of its cellular toxicity. The role of dissolution in the toxicity of ZnO nanoparticles was also investigated. Our results demonstrate that HepG2 cells exposed to 14–20 μg/ml ZnO nanoparticles for 12 h showed a decrease in cell viability and the mode of cell death induced by ZnO nanoparticles was apoptosis. They also induced DNA damage which was mediated by oxidative stress as evidenced by an increase in Fpg sensitive sites. Reactive oxygen species triggered a decrease in mitochondria membrane potential and an increase in the ratio of Bax/Bcl2 leading to mitochondria mediated pathway involved in apoptosis. In addition, ZnO nanoparticles activated JNK, p38 and induced p53Ser15 phosphorylation. However, apoptosis was found to be independent of JNK and p38 pathways. This study investigating the effects of ZnO nanoparticles in human liver cells has provided valuable insights into the mechanism of toxicity induced by ZnO nanoparticles.


Zinc oxide nanoparticles Human liver cells Mechanism of toxicity DNA damage Apoptosis MAPK Oxidative stress 



The authors thank CSIR, New Delhi for funding under its network project (NWP35) and supra institutional project (SIP-08). The funding from the Department of Science and Technology under the nanomission project—DST-NSTI grant (SR/S5/NM-01/2007) and UK India Education and Research Initiative (UKIERI) standard award to Indian Institute of Toxicology Research, Lucknow, India (DST/INT/UKIERI/SA/P-10/2008) and University of Bradford, Bradford, UK (SA 07-067) is duly acknowledged. The funding for the NanoLINEN project from the Department of Biotechnology, Government of India, under the NewINDIGO scheme is also acknowledged. Vyom Sharma thanks the Council of Scientific and Industrial Research (New Delhi) for the award of a Senior Research Fellowship.

Conflict of interest

The authors declare that there is no conflict of interest.


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Nanomaterial Toxicology GroupCSIR-Indian Institute of Toxicology ResearchLucknowIndia
  2. 2.Division of Medical Sciences, School of Life SciencesUniversity of BradfordBradfordUK
  3. 3.Gillings School of Global Public HealthUniversity of North CarolinaChapel HillUSA
  4. 4.Institute of Life SciencesAhmedabad UniversityAhmedabadIndia

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