Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Chinese Academy of Sciences, Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, P.R. China; University of Science and Technology of China, Hefei, Anhui 230026, P.R. China.
Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Chinese Academy of Sciences, Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, P.R. China.
J Environ Sci (China). 2019 Nov;85:94-106. doi: 10.1016/j.jes.2019.04.024. Epub 2019 May 22.
Titanium dioxide nanoparticles (TiO NPs) are subjected to various transformation processes (chemical, physical and biological processes) in the environment, potentially affecting their bioavailability and toxic properties. However, the size variation of TiO NPs during aging process and subsequent effects in mammalian cells are largely unknown. The aim of this study was to illustrate the adverse effects of TiO NPs in different sizes (5, 15 and <100 nm) during aging process on human-hamster hybrid (A) cells. There was an aging-time dependent enhancement of average hydrodynamic size in TiO NPs stock suspensions. The cytotoxicity of fresh TiO NPs increased in a size-dependent manner; in contrast, their genotoxicity decreased with the increasing sizes of NPs. No significant toxicity difference was observed in cells exposed to either fresh or 60 day-aged TiO NPs. Both Fresh and aged TiO NPs efficiently induced mitochondrial dysfunction and activated Caspase-3/7 in a size-dependent manner. Using mitochondrial-DNA deficient (ρ) A cells, we further discovered that mitochondrial dysfunction made significant contribution to the size-dependent toxicity induced by TiO NPs during the aging process. Taken together, our data indicated that TiO NPs could significantly induced the cytotoxicity and genotoxicity in an aging time-independent and size-dependent manner, which were triggered by mitochondrial dysfunction. Our study suggested the necessity to include size as an additional parameter for the cautious monitoring of TiO NPs disposal before entering the environment.
二氧化钛纳米粒子（TiO2 NPs）在环境中会经历各种转化过程（化学、物理和生物过程），这可能会影响它们的生物利用度和毒性。然而，TiO2 NPs 在老化过程中的粒径变化及其在哺乳动物细胞中的后续影响在很大程度上尚不清楚。本研究旨在阐明 TiO2 NPs 在不同粒径（5、15 和 <100nm）在老化过程中的不良影响对人仓鼠杂种（A）细胞的影响。TiO2 NPs 储备悬浮液的平均水动力粒径随老化时间的增加而增加。新鲜 TiO2 NPs 的细胞毒性呈粒径依赖性增加；相比之下，其遗传毒性随 NPs 粒径的增加而降低。暴露于新鲜或 60 天老化的 TiO2 NPs 的细胞未观察到明显的毒性差异。新鲜和老化的 TiO2 NPs 均能有效地诱导线粒体功能障碍，并在线粒体功能障碍的情况下激活 Caspase-3/7，呈粒径依赖性。使用线粒体 DNA 缺陷（ρ）A 细胞，我们进一步发现，线粒体功能障碍对 TiO2 NPs 在老化过程中引起的粒径依赖性毒性有重要贡献。综上所述，我们的数据表明，TiO2 NPs 可以在不依赖老化时间且呈粒径依赖性的方式下显著诱导细胞毒性和遗传毒性，这是由线粒体功能障碍引起的。我们的研究表明，在 TiO2 NPs 进入环境之前，有必要将粒径作为一个额外参数来谨慎监测其处理。
