TY - JOUR

T1 - Biomarkers of nucleic acid oxidation

T2 - A summary state-of-the-art

AU - Chao, Mu-Rong

AU - Evans, Mark D.

AU - Hu, Chiung-Wen

AU - Ji, Yunhee

AU - Møller, Peter

AU - Rossner, Pavel

AU - Cooke, Marcus S.

PY - 2021

Y1 - 2021

N2 - Oxidatively generated damage to DNA has been implicated in the pathogenesis of a wide variety of diseases. Increasingly, interest is also focusing upon the effects of damage to the other nucleic acids, RNA and the (2?deoxy-)ribonucleotide pools, and evidence is growing that these too may have an important role in disease. LCMS/MS has the ability to provide absolute quantification of specific biomarkers, such as 8-oxo-7,8-dihydro-2?deoxyGuo (8-oxodG), in both nuclear and mitochondrial DNA, and 8-oxoGuo in RNA. However, significant quantities of tissue are needed, limiting its use in human biomonitoring studies. In contrast, the comet assay requires much less material, and as little as 5 ?L of blood may be used, offering a minimally invasive means of assessing oxidative stress in vivo, but this is restricted to nuclear DNA damage only. Urine is an ideal matrix in which to non-invasively study nucleic acid-derived biomarkers of oxidative stress, and considerable progress has been made towards robustly validating these measurements, not least through the efforts of the European Standards Committee on Urinary (DNA) Lesion Analysis. For urine, LC-MS/MS is considered the gold standard approach, and although there have been improvements to the ELISA methodology, this is largely limited to 8oxodG. Emerging DNA adductomics approaches, which either comprehensively assess the totality of adducts in DNA, or map DNA damage across the nuclear and mitochondrial genomes, offer the potential to considerably advance our understanding of the mechanistic role of oxidatively damaged nucleic acids in disease.

AB - Oxidatively generated damage to DNA has been implicated in the pathogenesis of a wide variety of diseases. Increasingly, interest is also focusing upon the effects of damage to the other nucleic acids, RNA and the (2?deoxy-)ribonucleotide pools, and evidence is growing that these too may have an important role in disease. LCMS/MS has the ability to provide absolute quantification of specific biomarkers, such as 8-oxo-7,8-dihydro-2?deoxyGuo (8-oxodG), in both nuclear and mitochondrial DNA, and 8-oxoGuo in RNA. However, significant quantities of tissue are needed, limiting its use in human biomonitoring studies. In contrast, the comet assay requires much less material, and as little as 5 ?L of blood may be used, offering a minimally invasive means of assessing oxidative stress in vivo, but this is restricted to nuclear DNA damage only. Urine is an ideal matrix in which to non-invasively study nucleic acid-derived biomarkers of oxidative stress, and considerable progress has been made towards robustly validating these measurements, not least through the efforts of the European Standards Committee on Urinary (DNA) Lesion Analysis. For urine, LC-MS/MS is considered the gold standard approach, and although there have been improvements to the ELISA methodology, this is largely limited to 8oxodG. Emerging DNA adductomics approaches, which either comprehensively assess the totality of adducts in DNA, or map DNA damage across the nuclear and mitochondrial genomes, offer the potential to considerably advance our understanding of the mechanistic role of oxidatively damaged nucleic acids in disease.

KW - Oxidative stress

KW - DNA

KW - RNA

KW - Nucleotide pool

KW - Biomarkers

KW - DNA repair

KW - PERFORMANCE LIQUID-CHROMATOGRAPHY

KW - TANDEM MASS-SPECTROMETRY

KW - NUCLEOTIDE EXCISION-REPAIR

KW - LINKED-IMMUNOSORBENT-ASSAY

KW - GINGIVAL CREVICULAR FLUID

KW - ENDOGENOUS DNA ADDUCT

KW - IN-VITRO REPAIR

KW - COMET ASSAY

KW - HUMAN URINE

KW - MITOCHONDRIAL-DNA

U2 - 10.1016/j.redox.2021.101872

DO - 10.1016/j.redox.2021.101872

M3 - Journal article

C2 - 33579665

VL - 42

JO - Redox Biology

JF - Redox Biology

SN - 2213-2317

M1 - 101872

ER -