title: Toxic mechanisms of copper oxide nanoparticles in epithelial kidney cells.
abstract: CuO NPs have previously been reported as toxic to a range of cell cultures including kidney epithelial cells from the frog, Xenopus laevis (A6). Here we examine the molecular mechanisms affecting toxicity of Cu in different forms and particle sizes. A6 cells were exposed to ionic Cu (Cu2+) or CuO particles of three different sizes: CuO NPs of 6 nm (NP6), larger Poly-dispersed CuO NPs of <100 nm (Poly) and CuO Micro particles of <5 μm (Micro), at 200 μM, equal to 12.7 mg Cu/L. Poly was significantly more toxic than NP6, Micro and Cu2+ to A6 cells, causing DNA damage, decreased cell viability and levels of reduced glutathione (GSH) and eventually cell death. We show that ROS (Reactive Oxygen Species) generation plays a key role and occurs early in Poly toxicity as Poly-induced DNA damage and cell death could be mitigated by the antioxidant NAC (N-acetyl-cysteine). Here we propose a model of the sequence of events explaining Poly toxicity. Briefly, the events include: cellular uptake, most likely via endocytosis, production of ROS, which cause DNA damage that activates a signaling pathway which eventually leads to cell death, mainly via apoptosis.
authors: Dept. of Environmental, Social and Spatial Change, Roskilde University, Roskilde, Denmark. Electronic address: athitj@ruc.dk.
authors: Amalie
authors: A
authors: Thit
authors: Dept. of Environmental, Social and Spatial Change, Roskilde University, Roskilde, Denmark. Electronic address: selck@ruc.dk.
authors: Henriette
authors: H
authors: Selck
authors: Dept. of Science, Systems and Models, Roskilde University, Roskilde, Denmark. Electronic address: hfb@ruc.dk.
authors: Henning F
authors: HF
authors: Bjerregaard
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000633:toxicity*; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D053768:Metal Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D017382:Reactive Oxygen Species; D003300:Copper; D005978:Glutathione; C000520:cuprous oxide
keywords: Cell line; DNA damage; Mechanistic toxicology; Reactive oxygen species; Xenopus laevis