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

Yang Yu, Yuxiang Cui, Laura J. Niedernhofer, Yinsheng Wang

Research output: Contribution to journalReview articlepeer-review

57 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2008-2039
Number of pages32
JournalChemical research in toxicology
Volume29
Issue number12
DOIs
StatePublished - Dec 19 2016
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (R01 CA101864 and P01 AG043376).

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