title: Effect of silver nanoparticles on mitogen-activated protein kinases activation: role of reactive oxygen species and implication in DNA damage.
abstract: Large quantities of engineered nanoparticles (NP), such as nanosilver (AgNP), have been widely applied, leading to an increased exposure and potential health concerns. Herein, we have examined the ability of AgNP to induce reactive oxygen species (ROS), their role in genotoxic effects and the involvement of mitogen-activated protein kinases (MAPK). AgNP exposure induced ROS production in human epithelial embryonic cells which could be decreased by diphenyleneiodonium (DPI), an inhibitor of NADPH oxidases. Extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation, induced by AgNP, was an early response but not sustained in time. Furthermore, JNK and ERK activation could be inhibited by both DPI and a free radicals scavenger N-acetyl cysteine. We also investigated the role of MAPK in the DNA damage. Using a modified comet assay for the specific detection of hOGG1 sensitive sites, we showed that AgNP induced DNA oxidation after 30-min treatment, whereas no response was observed after 2h. In conclusion, AgNP seem to induce DNA damage via a mechanism involving ROS formation. The oxidative DNA damage observed was transient, likely due to DNA repair; furthermore, higher damage was achieved upon inhibition of ERK activation by pre-treatment with U0126, suggesting a role for ERK in DNA damage repair. Activation of different MAPK might play an important role in the NP toxicity outcomes; understanding this process may be helpful for the identification of NP toxicity.
authors.affiliation: Health Effects Laboratory, Environmental Chemistry Department, NILU-Norwegian Institute for Air Research, PO Box 100, 2027 Kjeller, Norway, Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, PO Box 1109 Blindern, 0317 Oslo, Norway, alessandra.rinna@odont.uio.no.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rinna
authors.affiliation: Health Effects Laboratory, Environmental Chemistry Department, NILU-Norwegian Institute for Air Research, PO Box 100, 2027 Kjeller, Norway.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Magdolenova
authors.affiliation: Health Effects Laboratory, Environmental Chemistry Department, NILU-Norwegian Institute for Air Research, PO Box 100, 2027 Kjeller, Norway.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hudecova
authors.affiliation: Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warszawa, Poland, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland and.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kruszewski
authors.affiliation: Department of Air Pollution and Noise, Norwegian Institute of Public Health, PO Box 4404 Nydalen, 0403 Oslo, Norway.
authors.forename: Magne
authors.initials: M
authors.lastname: Refsnes
authors.affiliation: Health Effects Laboratory, Environmental Chemistry Department, NILU-Norwegian Institute for Air Research, PO Box 100, 2027 Kjeller, Norway.
authors.forename: Maria
authors.initials: M
authors.lastname: Dusinska
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western; D020552:Comet Assay / Q000379:methods; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects*; D004847:Epithelial Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000633:toxicity*; D008854:Microscopy, Electron; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009580:Nitroblue Tetrazolium; D009861:Onium Compounds; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012834:Silver / Q000633:toxicity*
chemical_list: D009861:Onium Compounds; D017382:Reactive Oxygen Species; D009580:Nitroblue Tetrazolium; D012834:Silver; C007517:diphenyleneiodonium; D020928:Mitogen-Activated Protein Kinases