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Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
Oxidative DNA damage: mechanisms, mutation, and disease
Marcus S Cooke1, Mark D Evans, Miral Dizdaroglu
1Oxidative Stress Group, Department of Clinical Biochemistry, University of Leicester, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, LE2 7LX, UK. msc5@le.ac.uk
Abstract:
Oxidative DNA damage is an inevitable consequence of cellular metabolism, with a propensity for increased levels following toxic insult. Although more than 20 base lesions have been identified, only a fraction of these have received appreciable study, most notably 8-oxo-2'deoxyguanosine. This lesion has been the focus of intense research interest and been ascribed much importance, largely to the detriment of other lesions. The present work reviews the basis for the biological significance of oxidative DNA damage, drawing attention to the multiplicity of proteins with repair activities along with a number of poorly considered effects of damage. Given the plethora of (often contradictory) reports describing pathological conditions in which levels of oxidative DNA damage have been measured, this review critically addresses the extent to which the in vitro significance of such damage has relevance for the pathogenesis of disease. It is suggested that some shortcomings associated with biomarkers, along with gaps in our knowledge, may be responsible for the failure to produce consistent and definitive results when applied to understanding the role of DNA damage in disease, highlighting the need for further studies.
Insights
Oxidative DNA damage, a result of cell metabolism, has many forms, but research often focuses on just one. This review highlights other lesions and repair proteins, questioning the relevance of current findings for disease.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Oxidative DNA damage is a continuous process in cells, increasing with toxic exposure.
- Over 20 DNA lesions exist, but 8-oxo-2'deoxyguanosine receives disproportionate research attention.
- This focus may overlook the broader biological significance of other oxidative DNA lesions.
Purpose of the Study:
- To review the biological significance of oxidative DNA damage beyond 8-oxo-2'deoxyguanosine.
- To highlight the roles of various DNA repair proteins.
- To critically assess the in vitro relevance of oxidative DNA damage for disease pathogenesis.
Main Methods:
- Literature review of oxidative DNA damage and repair mechanisms.
- Critical analysis of studies linking DNA damage biomarkers to disease.
- Evaluation of the biological significance of various DNA lesions.
Main Results:
- Multiple proteins are involved in repairing diverse oxidative DNA lesions.
- The significance of some DNA damage effects may be underestimated.
- In vitro findings on oxidative DNA damage relevance to disease pathogenesis are often contradictory.
Conclusions:
- Current research may overemphasize 8-oxo-2'deoxyguanosine, neglecting other critical lesions.
- Inconsistent results in disease studies may stem from biomarker limitations and knowledge gaps.
- Further research is needed to clarify the role of diverse oxidative DNA damage in disease.
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