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USING PROTEOMICS TO IMPROVE RISK ASSESSMENT OF HUMAN EXPOSURE TO ENVIRONMENTAL AGENTS
Citation:
Winnik, W. M. USING PROTEOMICS TO IMPROVE RISK ASSESSMENT OF HUMAN EXPOSURE TO ENVIRONMENTAL AGENTS. Presented at 2004 EPA Science Forum "Healthy Communities and Ecosystems", Washington, D. C, June 1-3, 2004.
Description:
Using Proteomics to Improve Risk Assessment of Human Exposure to Environmental Agents.
Authors: Witold M. Winnik
Key Words (4): Proteomics, LC/MS, Western Blots, 1D and 2D gel electrophoresis, toxicity
The goal of this project is to use proteomics for the characterization of proteins in the framework of understanding mode of action for human relevance in risk assessment and for developing biomarkers to aid in exposure assessment. Large scale characterization of the entire proteome of a cell line, tissue or organ enables studies of protein-protein interactions, protein modification, and localization. A typical proteomics experiment involves using mass spectrometry (MS) analysis to allow a scientist to analyze protein spots that have been isolated on a 2D-gel, and subsequently to compare the proteomes of control/healthy and exposed/diseased cells. The aim is to reveal heretofore unknown mechanisms of disease or biochemical reactions. Recent advances in MS analysis, and its application in tandem, and in combination with high performance liquid chromatography (LC/MS/MS), have provided a multi-dimensional technique as a powerful tool for proteomics investigations to achieve protein identification and characterization at high levels of accuracy, both qualitatively and quantitatively. Applying such a tool will help answer many research questions that are a priority at the EPA. These include: (1) the Life Stages Study, to study the link between life stage and protein modifications, and changes in the function of genes critical to cellular homeostasis, such as cell-cycle progression-control genes and proteins, (2) the Drinking Water program, to enhance existing studies on the impact of arsenic and disinfection by-products on the induction of toxicity in the kidney, liver and gastrointestinal system, (3) the NHEERL P450/Conazole Harmonization Study, to determine the mechanism of toxicity and tumorigenesis of drugs that belong to the antifungal conazole family. An overarching theme in all these areas of research is believed to be protein oxidation, and this is being studied using the LC/MS/MS ProteomeX WorkstationTM. The data generated should help confirm mechanisms of action of reactive oxygen species on cellular targets leading to protein oxidation.