Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals
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Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals. / Møller, Peter; Jensen, Ditte Marie; Christophersen, Daniel Vest; Kermanizadeh, Ali; Jacobsen, Nicklas Raun; Hemmingsen, Jette Gjerke; Danielsen, Pernille Høgh; Karottki, Dorina Gabriela; Roursgaard, Martin; Cao, Yi; Jantzen, Kim; Klingberg, Henrik; Hersoug, Lars-Georg; Loft, Steffen.
In: Environmental and Molecular Mutagenesis, Vol. 56, No. 2, 03.2015, p. 97-110.Research output: Contribution to journal › Review › Research › peer-review
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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 - Copyright © 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 airway exposure to ENMs and oxidized DNA in lung 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., 2014. © 2014 Wiley Periodicals, Inc.
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 airway exposure to ENMs and oxidized DNA in lung 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., 2014. © 2014 Wiley Periodicals, Inc.
U2 - 10.1002/em.21899
DO - 10.1002/em.21899
M3 - Review
C2 - 25196723
VL - 56
SP - 97
EP - 110
JO - Environmental and Molecular Mutagenesis
JF - Environmental and Molecular Mutagenesis
SN - 0893-6692
IS - 2
ER -
ID: 162898235