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Inflammation and cancer: chemical approaches to mechanisms, imaging, and treatment.

Marnett LJ - J. Org. Chem. (2012)

Bottom Line: Chronic inflammation contributes to the etiology of multiple diseases, especially those associated with aging, such as cancer and cardiovascular disease.The current perspective summarizes our research on unsaturated fatty acid oxidation in the context of inflammation and cancer.In addition to understanding the consequences of DNA and protein modification by lipid electrophiles, our research has focused on the development of molecularly targeted agents to image and treat cancer.

View Article: PubMed Central - PubMed

Affiliation: A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA. larry.marnett@vanderbilt.edu

ABSTRACT
The inflammatory response represents a first line of defense against invading pathogens and is important to human health. Chronic inflammation contributes to the etiology of multiple diseases, especially those associated with aging, such as cancer and cardiovascular disease. The chemistry of the inflammatory response is complex and involves the generation of highly reactive oxidants and electrophiles designed to kill the pathogen as well as the release of small molecule and protein mediators of intercellular signaling, chemotaxis, vasoconstriction, and wound-healing. Oxidation of unsaturated fatty acids--either nonenzymatic or enzymatic--contributes to the inflammatory response and associated cellular pathologies. The current perspective summarizes our research on unsaturated fatty acid oxidation in the context of inflammation and cancer. In addition to understanding the consequences of DNA and protein modification by lipid electrophiles, our research has focused on the development of molecularly targeted agents to image and treat cancer.

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Repair of εdA by glycosylase-catalyzed base excisionrepair (BER) and by AlkB-catalyzed oxidation.
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fig12: Repair of εdA by glycosylase-catalyzed base excisionrepair (BER) and by AlkB-catalyzed oxidation.

Mentions: This appears true for many of the other exocyclicadducts depicted in Figure 10. Interestingly,εdA is a relatively efficient substrate for a base-excisionrepair enzyme, alkyladenineglycosylase, which removes the adductedbase and replaces it following excision of the deoxyribosyl unit.52 εdA is also substrate for an oxygenase,AlkB, that oxidizes the etheno ring to a vicinal diol, which decomposesto glyoxal with regeneration of dA (Figure 12).53 Thus exocyclic adducts can be removedby nucleotide-excision repair, base-excision repair, or direct repairof damaged DNA but the extent to which each pathway participates dependson the adduct.


Inflammation and cancer: chemical approaches to mechanisms, imaging, and treatment.

Marnett LJ - J. Org. Chem. (2012)

Repair of εdA by glycosylase-catalyzed base excisionrepair (BER) and by AlkB-catalyzed oxidation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3375764&req=5

fig12: Repair of εdA by glycosylase-catalyzed base excisionrepair (BER) and by AlkB-catalyzed oxidation.
Mentions: This appears true for many of the other exocyclicadducts depicted in Figure 10. Interestingly,εdA is a relatively efficient substrate for a base-excisionrepair enzyme, alkyladenineglycosylase, which removes the adductedbase and replaces it following excision of the deoxyribosyl unit.52 εdA is also substrate for an oxygenase,AlkB, that oxidizes the etheno ring to a vicinal diol, which decomposesto glyoxal with regeneration of dA (Figure 12).53 Thus exocyclic adducts can be removedby nucleotide-excision repair, base-excision repair, or direct repairof damaged DNA but the extent to which each pathway participates dependson the adduct.

Bottom Line: Chronic inflammation contributes to the etiology of multiple diseases, especially those associated with aging, such as cancer and cardiovascular disease.The current perspective summarizes our research on unsaturated fatty acid oxidation in the context of inflammation and cancer.In addition to understanding the consequences of DNA and protein modification by lipid electrophiles, our research has focused on the development of molecularly targeted agents to image and treat cancer.

View Article: PubMed Central - PubMed

Affiliation: A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Department of Biochemistry, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA. larry.marnett@vanderbilt.edu

ABSTRACT
The inflammatory response represents a first line of defense against invading pathogens and is important to human health. Chronic inflammation contributes to the etiology of multiple diseases, especially those associated with aging, such as cancer and cardiovascular disease. The chemistry of the inflammatory response is complex and involves the generation of highly reactive oxidants and electrophiles designed to kill the pathogen as well as the release of small molecule and protein mediators of intercellular signaling, chemotaxis, vasoconstriction, and wound-healing. Oxidation of unsaturated fatty acids--either nonenzymatic or enzymatic--contributes to the inflammatory response and associated cellular pathologies. The current perspective summarizes our research on unsaturated fatty acid oxidation in the context of inflammation and cancer. In addition to understanding the consequences of DNA and protein modification by lipid electrophiles, our research has focused on the development of molecularly targeted agents to image and treat cancer.

Show MeSH
Related in: MedlinePlus