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Oxidative DNA Damage: Mechanisms, Mutation, and Disease
Published
Author(s)
M S. Cooke, M D. Evans, M. Dizdaroglu, J Lunec
Abstract
Oxidative DNA damage is an inevitable consequence of cellular metabolism, with a propensity for increased levels following toxic insult. Although more than base lesions have been identified, only a fraction of these have received any appreciable study, most notably 8-oxo-2' deoxyguanosine. This lesion has been the focus of intense research interest, and been ascribed much importance, largely at 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 short-comings 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.
Citation
Faseb Journal
Volume
17
Issue
No. 10
Pub Type
Journals
Keywords
8-Hydroxyguanine, carcinogenesis, DNA repair, Hydroxyl radical, Mechanisms of Damage, Oxidative DNA Damage
Citation
Cooke, M.
, Evans, M.
, Dizdaroglu, M.
and Lunec, J.
(2003),
Oxidative DNA Damage: Mechanisms, Mutation, and Disease, Faseb Journal
(Accessed December 26, 2024)