title: Oxidative stress-induced cytotoxic and genotoxic effects of nano-sized titanium dioxide particles in human HaCaT keratinocytes.
abstract: Since nano-sized particles (NPs) are increasingly used in various fields of innovative biomedicine and industrial technologies, it is of importance to identify their potential human health risk. We investigated whether ROS-induced mitochondrial DNA damage is the mode of action of titanium dioxide-NPs (TiO2-NPs; ≤20 nm) to induce cytotoxic and genotoxic effects in human HaCaT keratinocytes in vitro. We showed that TiO2-NPs accumulate at the cell surface and are taken up by endocytosis. Micronucleus (MN) formation was found to be significantly maximal increased 24 h after treatment with 10 μg/ml and 48 h after treatment with 5 μg/ml TiO2-NPs about 1.8-fold respectively 2.2-fold of control. Mitochondrial DNA damage measured as "common deletion" was observed to be significantly 14-fold increased 72 h after treatment with 10 μg/ml TiO2-NPs when compared to control. Four hours after treatment with 5 and 50 μg/ml TiO2-NPs the level of ROS in HaCaT cells was found to be significantly increased about 7.5-fold respectively 16.7-fold of control. In conclusion, for the first time we demonstrate the induction of the mitochondrial "common deletion" in HaCaT cells following exposure to TiO2-NPs, which strongly suggests a ROS-mediated cytotoxic and genotoxic potential of NPs. However, the effects of the modification of TiO2-NPs, such as agglomeration, size distribution pattern and exposure time have to be further critically examined.
authors.affiliation: University of Rostock, Institute of Biological Sciences, Cell Biology and Biosystems Technology, Albert-Einstein-Straße 3, D-18059 Rostock, Germany. a.jaeger@fz-juelich.de
authors.forename: Alexandra
authors.initials: A
authors.lastname: Jaeger
authors.forename: Dieter G
authors.initials: DG
authors.lastname: Weiss
authors.forename: Ludwig
authors.initials: L
authors.lastname: Jonas
authors.forename: Ralf
authors.initials: R
authors.lastname: Kriehuber
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D015162:Micronucleus Tests; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000378:metabolism; D014025:Titanium / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D014466:Ultraviolet Rays
chemical_list: D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium