Department of Genetic Toxicology and Cancer Biology, National Institute of Biology , Ljubljana , Slovenia.
Nanotoxicology. 2011 Sep;5(3):341-53. doi: 10.3109/17435390.2010.507316. Epub 2010 Nov 10.
We investigated the genotoxic responses to two types of TiO2 nanoparticles (<25 nm anatase: TiO(2)-An, and <100 nm rutile: TiO2-Ru) in human hepatoma HepG2 cells. Under the applied exposure conditions the particles were agglomerated or aggregated with the size of agglomerates and aggregates in the micrometer range, and were not cytotoxic. TiO2-An, but not TiO2-Ru, caused a persistent increase in DNA strand breaks (comet assay) and oxidized purines (Fpg-comet). TiO2-An was a stronger inducer of intracellular reactive oxygen species (ROS) than TiO2-Ru. Both types of TiO2 nanoparticles transiently upregulated mRNA expression of p53 and its downstream regulated DNA damage responsive genes (mdm2, gadd45α, p21), providing additional evidence that TiO2 nanoparticles are genotoxic. The observed differences in responses of HepG2 cells to exposure to anatase and rutile TiO2 nanoparticles support the evidence that the toxic potential of TiO2 nanoparticles varies not only with particle size but also with crystalline structure.
我们研究了两种类型的 TiO2 纳米粒子（<25nm 锐钛矿：TiO(2)-An 和 <100nm 金红石：TiO2-Ru）对人肝癌 HepG2 细胞的遗传毒性反应。在应用的暴露条件下，这些颗粒聚集或团聚成微米级的团聚体和聚集体，且没有细胞毒性。TiO2-An 而非 TiO2-Ru 导致 DNA 链断裂（彗星试验）和氧化嘌呤（Fpg-彗星）持续增加。TiO2-An 比 TiO2-Ru 更能诱导细胞内活性氧物种（ROS）。两种类型的 TiO2 纳米粒子都能短暂地上调 p53 及其下游调控的 DNA 损伤反应基因（mdm2、gadd45α、p21）的 mRNA 表达，这为 TiO2 纳米粒子具有遗传毒性提供了更多证据。HepG2 细胞对锐钛矿和金红石 TiO2 纳米粒子暴露的反应差异表明，TiO2 纳米粒子的毒性潜力不仅与其粒径有关，还与其晶体结构有关。
