CORE--BIOTRANSFORMATION AND TOXICITY OF ENVIRONMENTAL CHEMICALS

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The general goals of the Biotransformation and Toxicity of Environmental Chemicals Research Core are to investigate the impact of environmental factors on chemical toxicity by examining biotransformation of environmental chemicals, the regulation of xenobiotic metabolizing enzymes, identification of molecular mechanisms of toxicity and carcinogenesis, and to identify natural chemoprotective agents and characterize their effects on cellular processes. The Biotransformation and Toxicity of Environmental Chemicals Research Core was formed in 1994 following reorganization of the Center. At that time, the Core was restructured and supervision of this core was given to Dr. CS Yang. In 1996, Dr. Paul Thomas was selected to serve as Co-Director because Dr. Yang became Deputy Director of the Center. The research interests of Core members fall into five general working areas which are Modulation of xenobiotic and steroid metabolism by environmental chemicals (by Drs. Conney and Lambert), Genetic polymorphisms of xenobiotic enzymes (Drs. Hong and Iba), Brain metabolism of chemicals and steroid hormones (Drs. Lowndes and Thomas), Molecular mechanisms of carcinogenesis and toxicity (Dr. Chen and Wei) and Protection against carcinogenesis and toxicity by dietary constituents, (Dr. Yang and Conney). Future goals of this core are to conduct greater in-depth mechanistic studies to understand how metabolism of chemicals affect its toxicity; to understand how xenobiotic metabolizing enzymes are regulated by environmental chemicals, dietary chemicals, and hormones; to extend investigations from animal tissues and proteins to humans; and to expand their genetic studies to understand how environmental chemicals alter genes and gene expression. This research core will promote further collaborative investigations and projects among researchers of the Center. Specific future studies include additional metabolism studies of environmental chemicals by P450 enzymes in different animal and human tissues; identify genetic polymorphisms associated with the metabolism of different environmental chemicals; characterize the xenobiotic metabolizing enzymes in human lung, esophagus, and liver; examine the effects of cigarette smoking and peroxisome proliferators on estradiol metabolism; perform additional structure-function studies on P450 2E1 and other xenobiotic metabolizing enzymes; study the regulation of CYP 3A expression; perform pharmacokinetic and pharmacodynamic studies on the chemoprotective effects of different food chemicals; examine the role of p53 gene in carcinogen-induced tumors; and use transgenic animal models to study the effects of environmental agents and oxidative stress on tumor formation and prevention.