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USING PROTEOMICS TO MONITOR PROTEIN EXPRESSION IN HUMAN CELLS EXPOSED TO CARCINOGENS
GE, Y., M. E. BRUNO, C. JONES, J. W. ALLEN, D. A. DELKER, R. D. OWEN, J. A. ROSS, AND A. B. DEANGELO. USING PROTEOMICS TO MONITOR PROTEIN EXPRESSION IN HUMAN CELLS EXPOSED TO CARCINOGENS. Presented at Public Health Application of Human Biomonitoring, RTP, NC, September 24 - 25, 2007.
To show that toxicoproteomics has the potential to be a powerful tool to detect the "fingerprints" of specific toxic effects.
People are continuously exposed exogenously to varying amounts of chemicals that have been shown to have carcinogenic properties in experimental systems. It has been estimated that exposure to environmental chemical carcinogens in the environment may contribute significantly to the etiology of a sizable fraction of human cancers. Molecular characterization of the proteome allows identification of protein biomarkers for human biomonitoring of chemical exposure and identification of protein indicators of biological effects. This proteomic characterization is required for a complete understanding of chemical exposure and effects, and is thus needed to understand the toxic mechanisms and modes of action for human health risk assessment. For this purpose, we have developed an integrated toxicoproteomic platform for the fractionation, detection and analysis of complex protein samples. With this 2D gel-based proteomic system about 10,000 proteins can be displayed, quantified and analyzed from a single biological sample. Application of this 2D-based proteomic system comprises a comprehensive approach to large-scale and high throughput protein expression profiling for the discovery of new biomarkers and toxicity signatures in target cells and organs. We performed 2D gel analysis of human colon epithelium cells exposed to carcinogens such as azoxymethane (AOM) and chemicals with potential carcinogenic properties such as tribromonitromethane (TBNM). Our results demonstrate that toxicoproteomics has the potential to be a powerful tool to detect the "fingerprints" of specific toxic effects, and thereby to facilitate the identification and development of biomarkers for risk assessment.