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Open AccessJournal ArticleDOI

Oxyradicals and DNA damage

Lawrence J. Marnett
- 01 Mar 2000 - 
- Vol. 21, Iss: 3, pp 361-370
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TLDR
The levels of oxidative DNA damage reported in many human tissues or in animal models of carcinogenesis exceed the levels of lesions induced by exposure to exogenous carcinogenic compounds, and it seems likely that oxidativeDNA damage is important in the etiology of many human cancers.
Abstract
A major development of carcinogenesis research in the past 20 years has been the discovery of significant levels of DNA damage arising from endogenous cellular sources. Dramatic improvements in analytical chemistry have provided sensitive and specific methodology for identification and quantitation of DNA adducts. Application of these techniques to the analysis of nuclear DNA from human tissues has debunked the notion that the human genome is pristine in the absence of exposure to environmental carcinogens. Much endogenous DNA damage arises from intermediates of oxygen reduction that either attack the bases or the deoxyribosyl backbone of DNA. Alternatively, oxygen radicals can attack other cellular components such as lipids to generate reactive intermediates that couple to DNA bases. Endogenous DNA lesions are genotoxic and induce mutations that are commonly observed in mutated oncogenes and tumor suppressor genes. Their mutagenicity is mitigated by repair via base excision and nucleotide excision pathways. The levels of oxidative DNA damage reported in many human tissues or in animal models of carcinogenesis exceed the levels of lesions induced by exposure to exogenous carcinogenic compounds. Thus, it seems likely that oxidative DNA damage is important in the etiology of many human cancers. This review highlights some of the major accomplishments in the study of oxidative DNA damage and its role in carcinogenesis. It also identifies controversies that need to be resolved. Unraveling the contributions to tumorigenesis of DNA damage from endogenous and exogenous sources represents a major challenge for the future.

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8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis.

TL;DR: The biomarker 8-OHdG or 8-oxodG has been a pivotal marker for measuring the effect of endogenous oxidative damage to DNA and as a factor of initiation and promotion of carcinogenesis and has been used to estimate the DNA damage in humans after exposure to cancer-causing agents.
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The Role of Oxidative Stress in Carcinogenesis

TL;DR: This review examines the evidence of cellular oxidants' involvement in the carcinogenesis process, and focuses on the mechanisms for production, cellular damage produced, and the role of signaling cascades by reactive oxygen species.
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Inflammation and cancer: How hot is the link?

TL;DR: The critical link between inflammation and cancer is described and observations imply that anti-inflammatory agents that suppress NF-kappaB or NF- kappaB-regulated products should have a potential in both the prevention and treatment of cancer.
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Oxidative Stress, Prooxidants, and Antioxidants: The Interplay

TL;DR: The importance of oxidative stress in the body growth and development as well as proteomic and genomic evidences of its relationship with disease development, incidence of malignancies and autoimmune disorders, increased susceptibility to bacterial, viral, and parasitic diseases are discussed.
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Inflammation and Cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation

TL;DR: Observations of mice genetically prone to inflammatory bowel disease also develop colorectal cancer especially in the presence of bacterial colonization offer compelling support for the role of inflammation in colon carcinogenesis.
References
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Journal ArticleDOI

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TL;DR: It is proposed that superoxide dismutase may protect vascular tissue stimulated to produce superoxide and NO under pathological conditions by preventing the formation of peroxynitrite.
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Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes.

TL;DR: This review provides a comprehensive summary on the chemical properties of 4-hydroxyalkenals and malonaldehyde, the mechanisms of their formation and their occurrence in biological systems and methods for their determination, as well as the many types of biological activities described so far.
Journal ArticleDOI

Instability and decay of the primary structure of DNA

TL;DR: The spontaneous decay of DNA is likely to be a major factor in mutagenesis, carcinogenesis and ageing, and also sets limits for the recovery of DNA fragments from fossils.
Journal ArticleDOI

Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG.

TL;DR: DCMP and dAMP are incorporated selectively opposite 8-oxodG with transient inhibition of chain extension occurring 3' to the modified base, and the potentially mutagenic insertion of dAMP is targeted exclusively to the site of the lesion.
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