ABSTRACT
I. Introduction ........................................................................................................................ 123 II. Genomics, Transcriptomics, and Gene Expression Profiling............................................. 125 III. Proteomics .......................................................................................................................... 126 IV. Metabolomics and Metabonomics...................................................................................... 129 V. Results ................................................................................................................................ 130
A. Microarray Analysis of Sulfur Mustard Exposure Reveals Potential Therapeutic Targets Confirmed by Protein Analysis ................................................. 130
B. Microarray Analysis of Phosgene Exposure Reveals Mechanisms of Toxicity that Correlate with Biochemical Data ..................................................... 132
C. Metabolomic Investigation of Liver and Blood Plasma Following Low-Level Exposure to VX Vapor ............................................................................ 137
VI. Conclusions ........................................................................................................................ 137 A. Biomarker Discovery.................................................................................................. 138 B. Mechanisms of Toxicity and Therapeutics................................................................. 138 C. Advanced Development of Therapeutics (FDA Approval)........................................ 139 D. Use of Animals in Research (Reduction, Refinement, and Replacement) ................ 139
VII. Summary............................................................................................................................. 139 References ..................................................................................................................................... 140
Since World War I, chemical warfare agents (CWAs) have been manufactured and stockpiled in numerous countries and remain a threat to both civilian and military personnel. CWAs have been used both in the context of military battle (e.g., World War I, the Iran-Iraq War) and in terrorist plots (e.g., Aum Shinrikyo attack on the Tokyo subway system) (Smart, 1997). CWAs are categorized into several classes based on chemical composition and toxicological effects. These include vesicants or blistering agents (sulfur mustard [HD], Lewisite [L]), blood agents (cyanide), choking
or pulmonary agents (phosgene [CG], chlorine [CL]), and nerve agents (tabun [GA], sarin [GB], soman [GD], cyclosarin [GF], VX). To protect military and civilian personnel from the threat posed by CWAs, research and development is ongoing into CWA detection methods, diagnosis of CWA exposure, treatment of CWA-exposed personnel, and decontamination of CWA-exposed personnel and equipment.
