A major thrust of the Vanderbilt Center in Molecular Toxicology involves the investigation of chemical and biological processes relating to the mode of action of genotoxic carcinogens. Genotoxins include environmental pollutants of industrial origin, pollutants of natural origin, substances that arise endogenously as products of oxidative metabolism, and drugs, foodstuffs and other substances to which man intentionally exposes himself. In order to understand the structural and mechanistic basis of DNA damage and mutagenesis, one must understand, 1) the types of adducts formed by the various mutagens and carcinogens and the other types of lesions such as those formed by oxidative metabolism, 2) the types of mutations produced by various polymerases and the mechanisms by which they arise, and 3) how the adducts alter the structure (i.e., conformation) of DNA and thereby degrade replication fidelity. At the same time, one needs to have an understanding of the extent and mechanism of recognition of the adducts (or the conformational alterations) by repair enzymes, p53 protein, transcription factors, and other proteins that interact with DNA in order to have a complete understanding of the biological properties of the adducts. Allied with these questions is the need to know the mechanisms of activation of carcinogens to form reactive species and the pathways by which the active species are detoxified. Some of these subjects are the focus of other research cores; close coordination exists between the activities of these other cores and those of the DNA Damage and Mutagenesis Core.
Showing the most recent 10 out of 712 publications
