title: Genotoxicity and gene expression modulation of silver and titanium dioxide nanoparticles in mice.
abstract: Recently, we showed that silver nanoparticles (AgNPs) caused apoptosis, necrosis and DNA strand breaks in different cell models in vitro. These findings warranted analyses of their relevance in vivo. We investigated the genotoxic potential and gene expression profiles of silver particles of nano- (Ag20, 20 nm) and submicron- (Ag200, 200 nm) size and titanium dioxide nanoparticles (TiO2-NPs, 21 nm) in selected tissues from exposed male mice including the gonades. A single dose of 5 mg/kg bw nanoparticles was administered intravenously to male mice derived from C57BL6 (WT) and 8-oxoguanine DNA glycosylase knock-out (Ogg1(-/-) KO). Testis, lung and liver were harvested one and seven days post-exposure and analyzed for DNA strand breaks and oxidized purines employing the Comet assay with Formamidopyrimidine DNA glycosylase (Fpg) treatment, and sperm DNA fragmentation by the sperm chromatin structure assay (SCSA). Based on an initial screening of a panel of 21 genes, seven genes were selected and their expression levels were analyzed in all lung and testis tissues sampled from all animals (n = 6 mice/treatment group) using qPCR. AgNPs, in particular Ag200, caused significantly increased levels of DNA strand breaks and alkali labile sites in lung, seven days post-exposure. Fpg-sensitive lesions were significantly induced in both testis and lung. The transcript level of some key genes; Atm, Rad51, Sod1, Fos and Mmp3, were significantly induced compared to controls, particularly in lung samples from Ag200-exposed KO mice. We conclude that the Ag200 causes genotoxicity and distinct gene expression patterns in selected DNA damage response and repair related genes.
authors.affiliation: a Department of Chemicals and Radiation, Division of Environmental Medicine , Norwegian Institute of Public Health , Oslo , Norway .
authors.forename: Nana
authors.initials: N
authors.lastname: Asare
authors.affiliation: a Department of Chemicals and Radiation, Division of Environmental Medicine , Norwegian Institute of Public Health , Oslo , Norway .
authors.forename: Nur
authors.initials: N
authors.lastname: Duale
authors.affiliation: a Department of Chemicals and Radiation, Division of Environmental Medicine , Norwegian Institute of Public Health , Oslo , Norway .|b Norwegian Directorate for Civil Protection , Tønsberg , Norway .
authors.forename: Hege H
authors.initials: HH
authors.lastname: Slagsvold
authors.affiliation: a Department of Chemicals and Radiation, Division of Environmental Medicine , Norwegian Institute of Public Health , Oslo , Norway .
authors.forename: Birgitte
authors.initials: B
authors.lastname: Lindeman
authors.affiliation: a Department of Chemicals and Radiation, Division of Environmental Medicine , Norwegian Institute of Public Health , Oslo , Norway .
authors.forename: Ann Karin
authors.initials: AK
authors.lastname: Olsen
authors.affiliation: c SGGW, Warsaw University of Life Sciences , Warsaw , Poland .
authors.forename: Joanna
authors.initials: J
authors.lastname: Gromadzka-Ostrowska
authors.affiliation: d Institute of Nuclear Chemistry and Technology, Center for Radiobiology and Biological Dosimetry , Warsaw , Poland .
authors.forename: Sylwia
authors.initials: S
authors.lastname: Meczynska-Wielgosz
authors.affiliation: e Department of Molecular Biology and Translational Research , Institute of Rural Health , Lublin , Poland , and.|f Faculty of Medicine , University of Information Technology and Management in Rzeszów , Rzeszów , Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kruszewski
authors.affiliation: a Department of Chemicals and Radiation, Division of Environmental Medicine , Norwegian Institute of Public Health , Oslo , Norway .
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brunborg
authors.affiliation: a Department of Chemicals and Radiation, Division of Environmental Medicine , Norwegian Institute of Public Health , Oslo , Norway .
authors.forename: Christine
authors.initials: C
authors.lastname: Instanes
mesh_terms: D000818:Animals; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D045647:DNA Glycosylases / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012834:Silver / Q000737:chemistry / Q000633:toxicity*; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*
chemical_list: C009495:titanium dioxide; D012834:Silver; D014025:Titanium; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse
keywords: Comet assay; DNA damage; Ogg1 deficiency; gene expression; genotoxicity; oxidative DNA lesions; reproductive toxicity