Occurrence, Biological Consequences, and Human Health Relevance of Oxidative Stress-Induced DNA Damage - PubMed (original) (raw)

Review

Occurrence, Biological Consequences, and Human Health Relevance of Oxidative Stress-Induced DNA Damage

Yang Yu et al. Chem Res Toxicol. 2016.

Abstract

A variety of endogenous and exogenous agents can induce DNA damage and lead to genomic instability. Reactive oxygen species (ROS), an important class of DNA damaging agents, are constantly generated in cells as a consequence of endogenous metabolism, infection/inflammation, and/or exposure to environmental toxicants. A wide array of DNA lesions can be induced by ROS directly, including single-nucleobase lesions, tandem lesions, and hypochlorous acid (HOCl)/hypobromous acid (HOBr)-derived DNA adducts. ROS can also lead to lipid peroxidation, whose byproducts can also react with DNA to produce exocyclic DNA lesions. A combination of bioanalytical chemistry, synthetic organic chemistry, and molecular biology approaches have provided significant insights into the occurrence, repair, and biological consequences of oxidatively induced DNA lesions. The involvement of these lesions in the etiology of human diseases and aging was also investigated in the past several decades, suggesting that the oxidatively induced DNA adducts, especially bulky DNA lesions, may serve as biomarkers for exploring the role of oxidative stress in human diseases. The continuing development and improvement of LC-MS/MS coupled with the stable isotope-dilution method for DNA adduct quantification will further promote research about the clinical implications and diagnostic applications of oxidatively induced DNA adducts.

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Figures

Figure 1

Figure 1

ROS-induced primary and secondary oxidation products of dG. [H] and [O] represent reduction and oxidation, respectively.

Figure 2

Figure 2

Pathways for hydroxyl radical-mediated oxidation of dT.

Figure 3

Figure 3

Oxidation pathways of 5-mdC. (a) ROS-induced oxidation of 5-mdC; (b) TET-mediated oxidation of 5-mdC.

Figure 4

Figure 4

Proposed mechanism for the formation of 5′R_- and 5′_S diastereomers of 8,5′-cyclo-2′-deoxyadenosine.

Figure 5

Figure 5

Structures of ROS-induced intrastrand cross-link lesions discussed in this review.

Figure 6

Figure 6

Inflammation-induced formation of hypochlorous acid (HOCl) and hypobromous acid (HOBR) and major nucleobase halogenation products. Myeloperoxidase can induce the formation of both HOCl and HOBr. The mechanism for the formation of HOBr by myeloperoxidase is different from that by eosinophil peroxidase.

Figure 7

Figure 7

Structures of representative lipid peroxidation (LPO) byproducts and DNA adducts induced by these byproducts.

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