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

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-TiO(2)), a more detailed view of the underlying mechanisms of this response needs to be established. Here the effects of nano-TiO(2) on the DNA damage response and DNA replication dynamics were investigated in human dermal fibroblasts. Specifically, the relationship between nano-TiO(2) and the DNA damage response pathways regulated by ATM/Chk2 and ATR/Chk1 were examined. The results show increased phosphorylation of H2AX, ATM, and Chk2 after exposure. In addition, nano-TiO(2) inhibited the overall rate of DNA synthesis and frequency of replicon initiation events in DNA combed fibers. Taken together, these results demonstrate that exposure to nano-TiO(2) activates the ATM/Chk2 DNA damage response pathway