Biomarkers of oxidative damage to DNA and repair

Abstract

Oxidative-stress-induced damage to DNA includes a multitude of lesions, many of which are mutagenic and have multiple roles in cancer and aging. Many lesions have been characterized by MS-based methods after extraction and digestion of DNA. These preparation steps may cause spurious base oxidation, which is less likely to occur with methods such as the comet assay, which are based on nicking of the DNA strand at modified bases, but offer less specificity. The European Standards Committee on Oxidative DNA Damage has concluded that the true levels of the most widely studied lesion, 8-oxodG (8-oxo-7,8-dihydro-2'-deoxyguanosine), in cellular DNA is between 0.5 and 5 lesions per 10(6) dG bases. Base excision repair of oxidative damage to DNA can be assessed by nicking assays based on oligonucleotides with lesions or the comet assay, by mRNA expression levels or, in the case of, e.g., OGG1 (8-oxoguanine DNA glycosylase 1), responsible for repair of 8-oxodG, by genotyping. Products of repair in DNA or the nucleotide pool, such as 8-oxodG, excreted into the urine can be assessed by MS-based methods and generally reflects the rate of damage. Experimental and population-based studies indicate that many environmental factors, including particulate air pollution, cause oxidative damage to DNA, whereas diets rich in fruit and vegetables or antioxidant supplements may reduce the levels and enhance repair. Urinary excretion of 8-oxodG, genotype and expression of OGG1 have been associated with risk of cancer in cohort settings, whereas altered levels of damage, repair or urinary excretion in case-control settings may be a consequence rather than the cause of the disease.

Telomeres in the Brain Cortex of Patients with Major Depressive Disorder

“…The OGG1 gene encodes the 8-oxoguanine DNA glycosylase I, which repairs oxidized DNA by eliminating 8-doxoG accumulated under the effects of ROS. Expression level of this gene is a validated biomarker for in vivo detection of chronic oxidative stress (Loft et al, 2008). Furthermore overexpression of OGG1 is a hallmark of the oxidative stress response activated in the aging human brain (Lu et al, 2004).…”

Boron doped diamond electrode pre-treatments effect on the electrochemical oxidation of dsDNA, DNA bases, nucleotides, homopolynucleotides and biomarker 8-oxoguanine

“…Fortunately, the importance of these lesions are underscored by the existence of mechanisms for their cellular repair, principally glycosylase activity that removes 8-oxoGua in both bacteria and yeast, and also in human cells [4][5][6].…”

Freshwater shrimp (Palaemonetes australis) as a potential bioindicator of crustacean health

“…There is some evidence to suggest there are two pathways for the removal of 8-oxodG adducts. Bases suffering oxidative damage are preferentially repaired by enzymes of the base excision repair (BER) pathway (Loft et al 2008). If the BER pathway is compromised a nucleotide excision repair (NER) pathway exists for the removal of the 8-oxo-dG adduct resulting in an observed reduction the amount of free 8-oxo-dG in the hemolymph.…”