Oxidative DNA damage: mechanisms, mutation, and disease.
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.
Cooke
Marcus S
MS
Oxidative 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
Evans
Mark D
MD
Dizdaroglu
Miral
M
Lunec
Joseph
J
D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
D018736:DNA Adducts; D017382:Reactive Oxygen Species