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

Journal article

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. and Loft, S. 2014. Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals. Environmental and Molecular Mutagenesis. Vol 56 (Issue 2), pp. 97 - 110. https://doi.org/10.1002/em.21899
AuthorsMøller, 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. and Loft, S.
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. Environ. Mol. Mutagen. 56:97–110, 2015.

Keywords8-oxodG; ; Diesel exhaust particles; ; FPG; ; HOGG1; ; Methylmethane sulfonate; ; Printex 90
Year2014
JournalEnvironmental and Molecular Mutagenesis
Journal citationVol 56 (Issue 2), pp. 97 - 110
PublisherWiley Online Library
ISSN0893-6692
1098-2280
Digital Object Identifier (DOI)https://doi.org/10.1002/em.21899
Web address (URL)http://www.scopus.com/inward/record.url?eid=2-s2.0-84925300353&partnerID=MN8TOARS
Output statusPublished
Publication dates05 Sep 2014
01 Mar 2015
Publication process dates
Accepted21 Aug 2014
Deposited12 Jun 2023
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