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. 2010 Dec 16:2010:929047.
doi: 10.4061/2010/929047.

The biological and metabolic fates of endogenous DNA damage products

Simon Wan Chan  1 , Peter C Dedon
Affiliations

The biological and metabolic fates of endogenous DNA damage products

Simon Wan Chan et al. J Nucleic Acids. .

Abstract

DNA and other biomolecules are subjected to damaging chemical reactions during normal physiological processes and in states of pathophysiology caused by endogenous and exogenous mechanisms. In DNA, this damage affects both the nucleobases and 2-deoxyribose, with a host of damage products that reflect the local chemical pathology such as oxidative stress and inflammation. These damaged molecules represent a potential source of biomarkers for defining mechanisms of pathology, quantifying the risk of human disease and studying interindividual variations in cellular repair pathways. Toward the goal of developing biomarkers, significant effort has been made to detect and quantify damage biomolecules in clinically accessible compartments such as blood and and urine. However, there has been little effort to define the biotransformational fate of damaged biomolecules as they move from the site of formation to excretion in clinically accessible compartments. This paper highlights examples of this important problem with DNA damage products.

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Figures

Figure 1
Figure 1
Nucleobase damage products.
Figure 2
Figure 2
2-Deoxyribose oxidation products.
Figure 3
Figure 3
Oxidation of substituted etheno adducts.
Figure 4
Figure 4
Formation and metabolism of M1dG.
Figure 5
Figure 5
Glyoxal adducts of DNA.
Figure 6
Figure 6
Reaction of 1,4-dioxo-2-butene to form bicyclic oxadiazabicyclo-(3.3.0) octaimine adducts.
Figure 7
Figure 7
Formation of DNA-protein cross-links during repair of 2-deoxyribonolactone abasic sites in DNA.
Figure 8
Figure 8
Reaction of lipid peroxidation products with lysine.
Figure 9
Figure 9
Lysine N-formylation by 3′-formylphosphate from 5′-oxidation of 2-deoxyribose.
Figure 10
Figure 10
Formation of glutathione adducts of 2-deoxyribose oxidation products.
See this image and copyright information in PMC

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