TY - JOUR

T1 - Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals

AU - Møller, Peter

AU - Jensen, Ditte Marie

AU - Christophersen, Daniel Vest

AU - Kermanizadeh, Ali

AU - Jacobsen, Nicklas Raun

AU - Hemmingsen, Jette Gjerke

AU - Danielsen, Pernille Høgh

AU - Karottki, Dorina Gabriela

AU - Roursgaard, Martin

AU - Cao, Yi

AU - Jantzen, Kim

AU - Klingberg, Henrik

AU - Hersoug, Lars-Georg

AU - Loft, Steffen

N1 - © 2014 Wiley Periodicals, Inc.

PY - 2015/3

Y1 - 2015/3

N2 - 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.

AB - 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.

KW - 8-Hydroxy-2'-Deoxyguanosine

KW - Animals

KW - Cells, Cultured/drug effects

KW - DNA Damage/drug effects

KW - DNA Glycosylases/biosynthesis

KW - Deoxyguanosine/analogs & derivatives

KW - Methyl Methanesulfonate/chemistry

KW - Nanostructures/chemistry

KW - Oxidative Stress/drug effects

KW - Vehicle Emissions/toxicity

U2 - 10.1002/em.21899

DO - 10.1002/em.21899

M3 - Review article

C2 - 25196723

VL - 56

SP - 97

EP - 110

JO - Environmental and molecular mutagenesis

JF - Environmental and molecular mutagenesis

SN - 0893-6692

IS - 2

ER -