Titanium dioxide nanoparticles activate the ATM-Chk2 DNA damage response in human dermal fibroblasts

Nanotoxicology. 2013 Sep;7(6):1111-9. doi: 10.3109/17435390.2012.710659. Epub 2012 Aug 23.


The use of nanoparticles in consumer products increases their prevalence in the environment and the potential risk to human health. Although recent studies have shown in vivo and in vitro toxicity of titanium dioxide nanoparticles (nano-TiO2), a more detailed view of the underlying mechanisms of this response needs to be established. Here, the effects of nano-TiO2 on the DNA damage response and DNA replication dynamics were investigated in human dermal fibroblasts. Specifically, the relationship between nano-TiO2 and the DNA damage response pathways regulated by ATM/Chk2 and ATR/Chk1 was examined. The results show increased phosphorylation of H2AX, ATM, and Chk2 after exposure. In addition, nano-TiO2 inhibited the overall rate of DNA synthesis and frequency of replicon initiation events in DNA-combed fibres. Taken together, these results demonstrate that exposure to nano-TiO2 activates the ATM/Chk2 DNA damage response pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Ataxia Telangiectasia Mutated Proteins / metabolism*
  • Cells, Cultured
  • Checkpoint Kinase 2 / genetics
  • Checkpoint Kinase 2 / metabolism*
  • Culture Media
  • DNA Damage / drug effects*
  • DNA Damage / physiology
  • Fibroblasts / drug effects*
  • Fibroblasts / physiology
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / toxicity*
  • Microscopy, Acoustic
  • Phosphorylation
  • Titanium / chemistry
  • Titanium / toxicity*


  • Culture Media
  • H2AX protein, human
  • Histones
  • titanium dioxide
  • Titanium
  • Checkpoint Kinase 2
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • CHEK2 protein, human