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Cited by 1,820Antioxidant Activity and Oxidative StressCarcinogens and Genotoxicity AssessmentCancer and biochemical research

The DOI matches its Crossref record; 195 of the 195 references it cites were found in a registry or an index.

Role of oxygen radicals in DNA damage and cancer incidence

Valko, Marian, Izakovic, Mario, Mazur, Milan, Rhodes, Christopher J., Telser, Joshua·2004·Molecular and Cellular Biochemistry
DOI 10.1023/b:mcbi.0000049134.69131.89
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Abstract

The development of cancer in humans and animals is a multistep process. The complex series of cellular and molecular changes participating in cancer development are mediated by a diversity of endogenous and exogenous stimuli. One type of endogenous damage is that arising from intermediates of oxygen (dioxygen) reduction - oxygen-free radicals (OFR), which attacks not only the bases but also the deoxyribosyl backbone of DNA. Thanks to improvements in analytical techniques, a major achievement in the understanding of carcinogenesis in the past two decades has been the identification and quantification of various adducts of OFR with DNA. OFR are also known to attack other cellular components such as lipids, leaving behind reactive species that in turn can couple to DNA bases. Endogenous DNA lesions are genotoxic and induce mutations. The most extensively studied lesion is the formation of 8-OH-dG. This lesion is important because it is relatively easily formed and is mutagenic and therefore is a potential biomarker of carcinogenesis. Mutations that may arise from formation of 8-OH-dG involve GC --> TA transversions. In view of these findings, OFR are considered as an important class of carcinogens. The effect of OFR is balanced by the antioxidant action of non-enzymatic antioxidants as well as antioxidant enzymes. Non-enzymatic antioxidants involve vitamin C, vitamin E, carotenoids (CAR), selenium and others. However, under certain conditions, some antioxidants can also exhibit a pro-oxidant mechanism of action. For example, beta-carotene at high concentration and with increased partial pressure of dioxygen is known to behave as a pro-oxidant. Some concerns have also been raised over the potentially deleterious transition metal ion-mediated (iron, copper) pro-oxidant effect of vitamin C. Clinical studies mapping the effect of preventive antioxidants have shown surprisingly little or no effect on cancer incidence. The epidemiological trials together with in vitro experiments suggest that the optimal approach is to reduce endogenous and exogenous sources of oxidative stress, rather than increase intake of anti-oxidants. In this review, we highlight some major achievements in the study of DNA damage caused by OFR and the role in carcinogenesis played by oxidatively damaged DNA. The protective effect of antioxidants against free radicals is also discussed.

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Crossref · 10.1023/b:mcbi.0000049134.69131.89

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Citations

Cites

Research works printed but not linked: 12

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Metadata

Authors
Valko, M., Izakovic, M., Mazur, M., Rhodes, C. J., & Telser, J.
Affiliations
  • University of Reading (GB)
  • Roosevelt University (US)
ORCID
Venue
Molecular and Cellular Biochemistry
Publisher
Springer Science and Business Media LLC
Published
2004-11
Volume
266
Issue
1-2
Pages
37-56
ISSN
  • 0300-8177 (ISSN-L)
  • 1573-4919
DOI
10.1023/b:mcbi.0000049134.69131.89
OpenAlex
W2165057232
Cited by
1,820
References
195
Citations by year
2026: 31 · 2025: 43 · 2024: 50 · 2023: 85 · 2022: 80 · 2021: 82 · 2020: 109 · 2019: 108 · 2018: 95 · 2017: 104 · 2016: 96 · 2015: 104 · 2014: 112 · 2013: 123 · 2012: 108
FWCI
32.15
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Molecular and Cellular Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • CentAUR (University of Reading) (acceptedVersion)
Funders
Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
Topics
  • Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
Keywords
oxygen free radicals, DNA damage, carcinogenesis, 8-oxoguanine, lipid peroxidation, antioxidant enzymes, non-enzymatic antioxidants, vitamin C, beta-carotene, pro-oxidant activity, oxidative stress, G:C to T:A transversions, cancer prevention
MeSH terms
Animals, Antioxidants, Cell Transformation, Neoplastic, DNA, DNA Damage, DNA Repair, Free Radicals, Humans, Neoplasms, Oxidation-Reduction, Incidence, Mutagenesis, Reactive Oxygen Species, Oxidative Stress, Lipid Metabolism

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