On the irrelevancy of hydroxyl radical to DNA damage from oxidative stress and implications for epigenetics

Abstract

Carbonate radical anion, not hydroxyl radical, is the principal reactive oxygen species generated from endogenous oxidative stress endowing epigenetic features to guanine oxidation products in DNA.

Long and short non-coding RNA and radiation response: a review

“…28 Historically, hydroxyl radicals have been considered the key species in DNA damage, however recent research has determined the key species is a carbonate radical anion formed in the Fenton reaction. 29 This carbonate radical anion is more abundant at physiological conditions than the hydroxyl radical and generates 8-oxo-7,8-dihydroguanine at GGG sites in DNA, which signals for DNA repair to begin. 29 Effects of radiation are a function of dose with a threshold, above which injury is imminent and below which most people, cells, tissues, or animals experience little to no acute effects.…”

“…29 This carbonate radical anion is more abundant at physiological conditions than the hydroxyl radical and generates 8-oxo-7,8-dihydroguanine at GGG sites in DNA, which signals for DNA repair to begin. 29 Effects of radiation are a function of dose with a threshold, above which injury is imminent and below which most people, cells, tissues, or animals experience little to no acute effects. 30 Radiation response is also determined by type of radiation source, volume of tissue irradiated, and time after irradiation.…”

Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways

“…The 8-oxoG lesions are genotoxic, and failure to remove 8-oxoG before replication occurs, results in the formation of G:C→T:A transversion mutations [ 43 ]. Furthermore, 8-oxoG is more easily oxidized than the parent guanine [ 44 ], and reacts with diverse oxyl radicals (CO 3 •− , • NO 2 , SO 4 •− , RO • ) [ 34 , 45 , 46 , 47 , 48 , 49 , 50 ], and peroxynitrite [ 51 , 52 ] to yield the stable end-products of four-electron oxidation of guanine, spiroiminodihydantoin (Sp) and 5-guanidinohydantoin (Gh) [ 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. Due to the presence of chiral carbon atoms, Sp and Gh exist in two diastereoisomeric S and R forms.…”

Targeted Antioxidants in Exercise-Induced Mitochondrial Oxidative Stress: Emphasis on DNA Damage

“…As a result, the hydroxyl free radical appreciably reacts with DNA bases at diffusion-controlled rates ( k ~ 5–8 × 10 9 M −1 s −1 for guanine [ 121 ]); potentially generating other end products, which can further propagate oxidative damage [ 122 ]. Interestingly, a recent supposition proposes that the carbonate radical anion as opposed to the hydroxyl free radical is the predominate radical formed from the Fenton reaction (Fe II (CO 3 )(OOH)(H 2 O) 2 → Fe III (OH) 3 (H 2 O) + CO 3 · − ) [ 123 , 124 ]. Given the reduction potentials of both the hydroxyl and carbonate radicals (2.4 and 1.6 V, respectively), it is not surprising that 2′-deoxyguanosine is a common outcome for these potent one-electron oxidants.…”

“…The role of exercise-induced mtDNA damage is enigmatic, and although generally considered harmful, the current lack of understanding associated with mtDNA allows scope for oxidative damage adducts to initiate or act as beneficial signals. One proposition is for oxidative modifications to DNA (e.g., 8-oxo-deoxyguanosine) to trigger the upregulation of repair genes and other genes that need to respond to the perturbations in cellular and/or mitochondrial redox state [ 124 ]. Additionally, DNA repair pathways help prevent heteroplasmy and maintain genome integrity; however, conjecture still surrounds whether these repair enzymes pre-exist in mitochondria at the time of damage or translocate into the mitochondria in response to damage signals [ 156 ].…”