Cited by 555DNA and Nucleic Acid ChemistryCarcinogens and Genotoxicity AssessmentDNA Repair Mechanisms

Oxidatively Generated Damage to the Guanine Moiety of DNA: Mechanistic Aspects and Formation in Cells

Cadet, Jean, Douki, Thierry, Ravanat, Jean-Luc·2008·Accounts of Chemical Research

Abstract

Nuclear DNA and other molecules in living systems are continuously exposed to endogenously generated oxygen species. Such species range from the unreactive superoxide radical (O2*-)the precursor of hydrogen peroxide (H2O2)to the highly reactive hydroxyl radical (*OH). Exogenous chemical and physical agents, such as ionizing radiation and the UVA component of solar light, can also oxidatively damage both the bases and the 2-deoxyribose moieties of cellular DNA. Over the last two decades, researchers have made major progress in understanding the oxidation degradation pathways of DNA that are most likely to occur from either oxidative metabolism or exposure to various exogenous agents. In the first part of this Account, we describe the mechanistic features of one-electron oxidation reactions of the guanine base in isolated DNA and related model compounds. These reactions illustrate the complexity of the various degradation pathways involved. Then, we briefly survey the analytical methods that can detect low amounts of oxidized bases and nucleosides in cells as they are formed. Recent data on the formation of oxidized guanine residues in cellular DNA following exposure to UVA light, ionizing radiation, and high-intensity UV pulses are also provided. We discuss these chemical reactions in the context of *OH radical, singlet oxygen, and two-quantum photoionization processes.

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Crossref · 10.1021/ar700245e

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  • An alternative mechanism for 6-TG-photosensitized formation of DPCs has been proposed based on reactivity of guanine radical cation with biological nucleophiles.

    “An alternative mechanism for the 6-TG-photosensitized formation of DPCs has been recently proposed (216) on the basis of the welldocumented reactivity of Gua •+ , the predominant oneelectron DNA oxidation transient radical formed, with relevant biological nucleophiles (111,134,136,217).”

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Authors
Cadet, J., Douki, T., & Ravanat, J.-L.
Affiliations
  • Université de Sherbrooke (CA)
  • Université Joseph Fourier (FR)
Venue
Accounts of Chemical Research
Published
2008-07-31
Volume
41
Issue
8
Pages
1075-1083
ISSN
  • 0001-4842 (ISSN-L)
  • 1520-4898
OpenAlex
W2077450957
Cited by
555
References
74
Citations by year
2026: 10 · 2025: 17 · 2024: 29 · 2023: 30 · 2022: 25 · 2021: 45 · 2020: 31 · 2019: 33 · 2018: 28 · 2017: 31 · 2016: 28 · 2015: 34 · 2014: 31 · 2013: 26 · 2012: 37
FWCI
16.47
Type
journal article
Language
en
Open access
closed
Locations
  • Accounts of Chemical Research (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
guanine oxidation, oxidative DNA damage, hydroxyl radicals, superoxide, hydrogen peroxide, one-electron oxidation, singlet oxygen, UVA, ionizing radiation, oxidative metabolism
MeSH terms
Animals, Cells, DNA, DNA Damage, Electrons, Guanine, Humans, Oxidation-Reduction

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