Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
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.
纳米颗粒在消费产品中的应用增加了它们在环境中的普遍性和对人类健康的潜在风险。尽管最近的研究表明了二氧化钛纳米颗粒（nano-TiO2）的体内和体外毒性，但需要建立更详细的关于这种反应的潜在机制的观点。在这里，研究了纳米二氧化钛对人真皮成纤维细胞中 DNA 损伤反应和 DNA 复制动力学的影响。具体来说，研究了纳米二氧化钛与 ATM/Chk2 和 ATR/Chk1 调节的 DNA 损伤反应途径之间的关系。结果表明，暴露后 H2AX、ATM 和 Chk2 的磷酸化增加。此外，纳米二氧化钛抑制了 DNA 梳纤维中整体 DNA 合成速率和复制起始事件的频率。总之，这些结果表明，暴露于纳米二氧化钛会激活 ATM/Chk2 DNA 损伤反应途径。
