title: Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals.
abstract: Increased levels of oxidatively damaged DNA have been documented in studies of metal, metal oxide, carbon-based and ceramic engineered nanomaterials (ENMs). In particular, 8-oxo-7,8-dihydroguanine-2'-deoxyguanosine (8-oxodG) is widely assessed as a DNA nucleobase oxidation product, measured by chromatographic assays, antibody-based methods or the comet assay with DNA repair enzymes. However, spurious oxidation of DNA has been a problem in certain studies applying chromatographic assays, yielding high baseline levels of 8-oxodG. Antibody-based assays detect high 8-oxodG baseline levels, related to cross-reactivity with other molecules in cells. This review provides an overview of efforts to reliably detect oxidatively damaged DNA and a critical assessment of the published studies on DNA damage levels. Animal studies with high baseline levels of oxidatively damaged DNA are more likely to show positive associations between exposure to ENMs and oxidized DNA in tissue than studies showing acceptable baseline levels (odds ratio = 12.1, 95% confidence interval: 1.2-124). Nevertheless, reliable studies indicate that intratracheal instillation of nanosized carbon black is associated with increased levels of oxidatively damaged DNA in lung tissue. Oral exposure to nanosized carbon black, TiO2 , carbon nanotubes and ZnO is associated with elevated levels of oxidatively damaged DNA in tissues. These observations are supported by cell culture studies showing concentration-dependent associations between ENM exposure and oxidatively damaged DNA measured by the comet assay. Cell culture studies show relatively high variation in the ability of ENMs to oxidatively damage DNA; hence, it is currently impossible to group ENMs according to their DNA damaging potential.
authors.affiliation: Department of Public Health, Section of Environmental Health, University of Copenhagen, Copenhagen K, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
authors.forename: Ditte Marie
authors.initials: DM
authors.lastname: Jensen
authors.forename: Daniel Vest
authors.initials: DV
authors.lastname: Christophersen
authors.forename: Ali
authors.initials: A
authors.lastname: Kermanizadeh
authors.forename: Nicklas Raun
authors.initials: NR
authors.lastname: Jacobsen
authors.forename: Jette Gjerke
authors.initials: JG
authors.lastname: Hemmingsen
authors.forename: Pernille Høgh
authors.initials: PH
authors.lastname: Danielsen
authors.forename: Dorina Gabriela
authors.initials: DG
authors.lastname: Karottki
authors.forename: Martin
authors.initials: M
authors.lastname: Roursgaard
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.forename: Kim
authors.initials: K
authors.lastname: Jantzen
authors.forename: Henrik
authors.initials: H
authors.lastname: Klingberg
authors.forename: Lars-Georg
authors.initials: LG
authors.lastname: Hersoug
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects*; D045647:DNA Glycosylases / Q000096:biosynthesis; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry; D008741:Methyl Methanesulfonate / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity
chemical_list: D001335:Vehicle Emissions; D000080242:8-Hydroxy-2'-Deoxyguanosine; D008741:Methyl Methanesulfonate; D045647:DNA Glycosylases; D003849:Deoxyguanosine
keywords: 8-oxodG; FPG; Printex 90; diesel exhaust particles; hOGG1; methylmethane sulfonate