Measurement and meaning of oxidatively modified DNA lesions in urine. 2008

Marcus S Cooke, and Ryszard Olinski, and Steffen Loft, and
Radiation and Oxidative Stress Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom. msc5@le.ac.uk

BACKGROUND Oxidatively generated damage to DNA has been implicated in the pathogenesis of a wide variety of diseases. The noninvasive assessment of such damage, i.e., in urine, and application to large-scale human studies are vital to understanding this role and devising intervention strategies. METHODS We have reviewed the literature to establish the status quo with regard to the methods and meaning of measuring DNA oxidation products in urine. RESULTS Most of the literature focus upon 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and whereas a large number of these reports concern clinical conditions, there remains (a) lack of consensus between methods, (b) possible contribution from diet and/or cell death, (c) no definitive DNA repair source of urinary 2'-deoxyribonucleoside lesions, and (d) no reference ranges for healthy or diseased individuals. CONCLUSIONS The origin of 8-oxodG is not identified; however, recent cell culture studies suggest that the action of Nudix hydrolase(s) on oxidative modification of the nucleotide pool is a likely candidate for the 8-oxodG found in urine and, potentially, of other oxidized 2'-deoxyribonucleoside lesions. Literature reports suggest that diet and cell death have minimal, if any, influence upon urinary levels of 8-oxodG and 8-oxo-7,8-dihydroguanine, although this should be assessed on a lesion-by-lesion basis. Broadly speaking, there is consensus between chromatographic techniques; however, ELISA approaches continue to overestimate 8-oxodG levels and is not sufficiently specific for accurate quantification. With increasing numbers of lesions being studied, it is vital that these fundamental issues are addressed. We report the formation of the European Standards Committee on Urinary (DNA) Lesion Analysis whose primary goal is to achieve consensus between methods and establish reference ranges in health and disease.

UI MeSH Term Description Entries
D003849 Deoxyguanosine A nucleoside consisting of the base guanine and the sugar deoxyribose.
D004032 Diet Regular course of eating and drinking adopted by a person or animal. Diets
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000080242 8-Hydroxy-2'-Deoxyguanosine Common oxidized form of deoxyguanosine in which C-8 position of guanine base has a carbonyl group. 2'-Deoxy-7,8-Dihydro-8-Oxoguanosine,2'-Deoxy-8-Hydroxyguanosine,2'-Deoxy-8-Oxo-7,8-Dihydroguanosine,2'-Deoxy-8-Oxoguanosine,7,8-Dihydro-8-Oxo-2'-Deoxyguanosine,7-Hydro-8-Oxodeoxyguanosine,8-Hydroxydeoxyguanosine,8-Oxo-2'-Deoxyguanosine,8-Oxo-7,8-Dihydro-2'-Deoxyguanosine,8-Oxo-7,8-Dihydrodeoxyguanosine,8-Oxo-7-Hydrodeoxyguanosine,8-Oxo-Deoxyguanosine,8OHdG,8-OH-dG,8-oxo-dG,8-oxo-dGuo,8-oxodG,8-oxodGuo,2' Deoxy 7,8 Dihydro 8 Oxoguanosine,2' Deoxy 8 Hydroxyguanosine,2' Deoxy 8 Oxo 7,8 Dihydroguanosine,2' Deoxy 8 Oxoguanosine,7 Hydro 8 Oxodeoxyguanosine,7,8 Dihydro 8 Oxo 2' Deoxyguanosine,8 Hydroxy 2' Deoxyguanosine,8 Hydroxydeoxyguanosine,8 Oxo 2' Deoxyguanosine,8 Oxo 7 Hydrodeoxyguanosine,8 Oxo 7,8 Dihydro 2' Deoxyguanosine,8 Oxo 7,8 Dihydrodeoxyguanosine,8 Oxo Deoxyguanosine
D016923 Cell Death The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. Death, Cell
D018384 Oxidative Stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). Anti-oxidative Stress,Antioxidative Stress,DNA Oxidative Damage,Nitro-Oxidative Stress,Oxidative Cleavage,Oxidative DNA Damage,Oxidative Damage,Oxidative Injury,Oxidative Nitrative Stress,Oxidative Stress Injury,Oxidative and Nitrosative Stress,Stress, Oxidative,Anti oxidative Stress,Anti-oxidative Stresses,Antioxidative Stresses,Cleavage, Oxidative,DNA Damage, Oxidative,DNA Oxidative Damages,Damage, DNA Oxidative,Damage, Oxidative,Damage, Oxidative DNA,Injury, Oxidative,Injury, Oxidative Stress,Nitrative Stress, Oxidative,Nitro Oxidative Stress,Nitro-Oxidative Stresses,Oxidative Cleavages,Oxidative DNA Damages,Oxidative Damage, DNA,Oxidative Damages,Oxidative Injuries,Oxidative Nitrative Stresses,Oxidative Stress Injuries,Oxidative Stresses,Stress Injury, Oxidative,Stress, Anti-oxidative,Stress, Antioxidative,Stress, Nitro-Oxidative,Stress, Oxidative Nitrative,Stresses, Nitro-Oxidative

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