Human Toxicogenomic Analysis Of The Monohaloacetic Acids

The goal of this project was to generate the first human toxicogenomic structure-activity relationship analysis comparing the monohaloacetic acids (monoHAAs). The specific objectives of this project and the chapters in which the detailed information is located is included in the following list. 1. Determine the DNA repair kinetics for iodoacetic, bromoacetic and chloroacetic acids in Chinese hamster ovary (CHO) cells (Chapter 6). 2. Determine the chronic cytotoxicity of iodoacetic acid (IAA), bromoacetic acid (BAA) and chloroacetic acid (CAA) to non-transformed normal human embryonic cells (Chapter 3). 3. Compare the cytotoxic sensitivity of human cells with that of CHO cells (Chapter 3). 4. Determine the acute genomic DNA damaging capacity of IAA, BAA and CAA to nontransformed, normal human embryonic cells (Chapter 3). 5. Compare the genotoxic sensitivity of human cells with that of CHO cells (Chapter 3). 6. Using gene array technologies, determine if nontoxic concentrations of each monoHAA differentially alters the expression of human genes involved in DNA damage/repair and human toxic responses (Chapters 2, 4, 5). 7. Determine the human functional gene assemblies and metabolic pathways that are altered after exposure to monoHAAs (Chapters 5, 7). 8. Explore if these gene expression changes may ultimately result in human disease and if specific gene functional groups may lead to the development human biomarkers (Chapter 5).