title: Copper-based nanoparticles induce high toxicity in leukemic HL60 cells.
abstract: 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.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 83 Huddinge, Stockholm, Sweden.
authors.forename: Ylva
authors.initials: Y
authors.lastname: Rodhe
authors.affiliation: KTH Royal Institute of Technology, Division of Surface and Corrosion Science, School of Chemical Science and Engineering, SE-100 44 Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Skoglund
authors.affiliation: KTH Royal Institute of Technology, Division of Surface and Corrosion Science, School of Chemical Science and Engineering, SE-100 44 Stockholm, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Odnevall Wallinder
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, SE-141 83 Huddinge, Stockholm, Sweden.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Potácová
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 83 Huddinge, Stockholm, Sweden. Electronic address: lennart.moller@ki.se.
authors.forename: Lennart
authors.initials: L
authors.lastname: Möller
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000633:toxicity*; D004249:DNA Damage; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia; D053768:Metal Nanoparticles / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects; D009336:Necrosis / Q000139:chemically induced; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D003300:Copper; C029892:cupric chloride; C030973:cupric oxide
keywords: Cu; CuO; Cytotoxicity; Mitochondrial damage; Nanoparticles; Oxidative stress