Rodhe Ylva, Skoglund Sara, Odnevall Wallinder Inger, Potácová Zuzana, Möller Lennart
Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 83 Huddinge, Stockholm, Sweden.
KTH Royal Institute of Technology, Division of Surface and Corrosion Science, School of Chemical Science and Engineering, SE-100 44 Stockholm, Sweden.
Toxicol In Vitro. 2015 Oct;29(7):1711-9. doi: 10.1016/j.tiv.2015.05.020. Epub 2015 May 28.
From the increasing societal use of nanoparticles (NPs) follows the necessity to understand their potential toxic effects. This requires an in-depth understanding of the relationship between their physicochemical properties and their toxicological behavior. The aim of the present work was to study the toxicity of Cu and CuO NPs toward the leukemic cell line HL60. The toxicity was explored in terms of mitochondrial damage, DNA damage, oxidative DNA damage, cell death and reactive oxygen species (ROS) formation. Particle characteristics and copper release were specifically investigated in order to gain an improved understanding of prevailing toxic mechanisms. The Cu NPs revealed higher toxicity compared with both CuO NPs and dissolved copper (CuCl2), as well as a more rapid copper release compared with CuO NPs. Mitochondrial damage was induced by Cu NPs already after 2 h exposure. Cu NPs induced oxidation at high levels in an acellular ROS assay, and a small increase of intracellular ROS was observed. The increase of DNA damage was limited. CuO NPs did not induce any mitochondrial damage up to 6 h of exposure. No acellular ROS was induced by the CuO NPs, and the levels of intracellular ROS and DNA damage were limited after 2 h exposure. Necrosis was the main type of cell death observed after 18 h exposure to CuO NP and dissolved copper.
随着纳米颗粒（NPs）在社会上的使用日益增加，有必要了解它们潜在的毒性作用。这需要深入了解其物理化学性质与毒理学行为之间的关系。本研究的目的是研究铜和氧化铜纳米颗粒对白血病细胞系HL60的毒性。从线粒体损伤、DNA损伤、氧化性DNA损伤、细胞死亡和活性氧（ROS）形成等方面探讨了毒性。特别研究了颗粒特性和铜释放情况，以便更好地理解主要的毒性机制。与氧化铜纳米颗粒和溶解铜（CuCl2）相比，铜纳米颗粒显示出更高的毒性，并且与氧化铜纳米颗粒相比，铜释放更快。暴露2小时后，铜纳米颗粒就已诱导线粒体损伤。在无细胞ROS测定中，铜纳米颗粒在高水平下诱导氧化，并且观察到细胞内ROS略有增加。DNA损伤的增加有限。暴露6小时内，氧化铜纳米颗粒未诱导任何线粒体损伤。氧化铜纳米颗粒未诱导无细胞ROS产生，暴露2小时后，细胞内ROS水平和DNA损伤有限。坏死是暴露于氧化铜纳米颗粒和溶解铜18小时后观察到的主要细胞死亡类型。
