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

doi:10.1002/em.21899

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

Section of Environmental Health

45 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 language	English
Journal	Environmental and Molecular Mutagenesis
Volume	56
Issue number	2
Pages (from-to)	97-110
Number of pages	14
ISSN	0893-6692
DOIs	https://doi.org/10.1002/em.21899
Publication status	Published - 1 Mar 2015

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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

Møller, P , Jensen, DM, Christophersen, DV, Kermanizadeh, A, Jacobsen, NR, Hemmingsen, JG, Danielsen, PH, Karottki, DG, 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, vol. 56, no. 2, pp. 97-110. https://doi.org/10.1002/em.21899

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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.",

author = "Peter M{\o}ller and Jensen, {Ditte Marie} and Christophersen, {Daniel Vest} and Ali Kermanizadeh and Jacobsen, {Nicklas Raun} and Hemmingsen, {Jette Gjerke} and Danielsen, {Pernille H{\o}gh} and Karottki, {Dorina Gabriela} and Martin Roursgaard and Yi Cao and Kim Jantzen and Henrik Klingberg and Lars-Georg Hersoug and Steffen Loft",

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doi = "10.1002/em.21899",

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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

PY - 2015/3/1

Y1 - 2015/3/1

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.

U2 - 10.1002/em.21899

DO - 10.1002/em.21899

M3 - Review

C2 - 25196723

SN - 0893-6692

VL - 56

SP - 97

EP - 110

JO - Environmental and Molecular Mutagenesis

JF - Environmental and Molecular Mutagenesis

IS - 2

ER -

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

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