This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Project 3 is developing methods to quantify oxidative modifications in DNA, proteins, and metabolites. We will focus on introducing 14C isotope labels into biological molecules in order to characterize pathways and biomarkers of relevance to human disease. This labeling is done by either dosing cells or animals with a labeled building block such as an amino acid for incorporation into proteins or a nucleoside for synthesis of DNA. Two main objectives of Project 3 are: (1) characterization of nucleotide pool oxidation products that are incorporated into DNA and RNA and (2) chlorination of proteins by HOCl produced by myeloperoxidase during the activation of white blood cells. Completion of these objectives will enable progress towards the general goal of quantifying the metabolic flux of molecules produced as a result of oxidative stress which may be related to cancer, diabetes, arteriosclerosis and numerous aging-related diseases.
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