Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals

Peter Møller, Ditte Marie Jensen, Daniel Vest Christophersen, Ali Kermanizadeh, Nicklas Raun Jacobsen, Jette Gjerke Hemmingsen, Pernille Høgh Danielsen, Dorina Gabriela Karottki, Martin Roursgaard, Yi Cao, Kim Jantzen, Henrik Klingberg, Lars-Georg Hersoug, Steffen Loft

Research output: Contribution to journalReview article

42 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)97-110
Number of pages14
JournalEnvironmental and Molecular Mutagenesis
Volume56
Issue number2
DOIs
Publication statusPublished - Mar 2015

Keywords

  • Animals
  • Cells, Cultured/drug effects
  • DNA Damage/drug effects
  • DNA Glycosylases/biosynthesis
  • Deoxyguanosine/analogs & derivatives
  • Methyl Methanesulfonate/chemistry
  • Nanostructures/chemistry
  • Oxidative Stress/drug effects
  • Vehicle Emissions/toxicity

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  • Cite this

    Møller, P., Jensen, D. M., Christophersen, D. V., Kermanizadeh, A., Jacobsen, N. R., Hemmingsen, J. G., Danielsen, P. H., Karottki, D. G., Roursgaard, M., Cao, Y., Jantzen, K., Klingberg, H., Hersoug, L-G., & Loft, S. (2015). Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals. Environmental and Molecular Mutagenesis, 56(2), 97-110. https://doi.org/10.1002/em.21899