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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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Related in: MedlinePlus

Random mutagenesis experiments with MDA.A single-stranded M13 bacteriophage genome was reacted with MDA torandomly introduce adducts. The adducted vector was replicated in E. coli. and mutations were identified by a combinationof screening for mutants and DNA sequencing.41
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fig5: Random mutagenesis experiments with MDA.A single-stranded M13 bacteriophage genome was reacted with MDA torandomly introduce adducts. The adducted vector was replicated in E. coli. and mutations were identified by a combinationof screening for mutants and DNA sequencing.41

Mentions: The diversityof adducts illustrated in Figure 4 renderedit difficult to directly relate adduct structure to particular mutationsinduced by MDA treatment of an intact cell. Direct reaction of MDAwith plasmid DNA followed by replication in E. coli demonstrated that mutations were induced at dG, dA, and dC residues(primarily dG→dT transversions, dA→dG transitions, anddC→dT transitions, respectively) (Figure 5).41


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

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

Random mutagenesis experiments with MDA.A single-stranded M13 bacteriophage genome was reacted with MDA torandomly introduce adducts. The adducted vector was replicated in E. coli. and mutations were identified by a combinationof screening for mutants and DNA sequencing.41
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Random mutagenesis experiments with MDA.A single-stranded M13 bacteriophage genome was reacted with MDA torandomly introduce adducts. The adducted vector was replicated in E. coli. and mutations were identified by a combinationof screening for mutants and DNA sequencing.41
Mentions: The diversityof adducts illustrated in Figure 4 renderedit difficult to directly relate adduct structure to particular mutationsinduced by MDA treatment of an intact cell. Direct reaction of MDAwith plasmid DNA followed by replication in E. coli demonstrated that mutations were induced at dG, dA, and dC residues(primarily dG→dT transversions, dA→dG transitions, anddC→dT transitions, respectively) (Figure 5).41

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