Blood Biomarkers for Assessing the Exposure and Response of Mammals to Chemical and Biological Agents.

摘要

We aimed to develop strategies for performing quantitative analyses of organ-specific blood biomarkers by: (1) developing better software for analyzing dynamically changing transcriptomes; (2) analyzing blood and multiple organs/tissues of animals from three inbred mouse strains exposed to the toxins acetaminophen and carbon tetrachloride for transcriptomes, proteins and miRNA biomarkers.; (3) establishing MRM mass spectrometry assays for at least 25 liver- specific blood proteins based on the acetaminophen, CCL4, and other model systems of interest; (4) analyzing blood and tissue of animals from three inbred mouse strains exposed to the toxins acetaminophen and carbon tetrachloride for protein biomarkers using proteomics technologies, including MRM; 5) Analyzing time course experiments of rat tissues and blood exposed to VX; and 6) Developing new technologies for developing protein-capture agents and the analyses of single protein molecules. Although discovery and validation of organ-specific biomarkers are challenging from a technical perspective, we made considerable progress towards achieving our stated aims.