Dr. Joanna Groden, who has moved from the Ecogenetics Core, directs the Genetic Toxicology Research Core which comprises six researchers, Drs. Joanna Groden (human genetics of cancer susceptibility), Dixon (cellular responses to DNA damage), Abdel-Malek (radiation induced responses in melanocytes), Paquin (gene amplification in yeast), Talaska (DNA adducts as biomarkers) and Warshawsky (metabolism of polycyclic compounds). The goals of this Research Core are to investigate the molecular mechanisms by which genotoxic environmental agents are metabolized to toxic intermediates; how genotoxic agents damage DNA; how DNA damage leads to mutation; how some cellular responses function to prevent mutagenesis (e.g., DNA repair and cell cycle arrest). Each of these aims is said to fit within the goals of the center as a whole in that they can be related to the """"""""impact of genetic diversity on the response of the individual to toxic environmental agents."""""""" In the previous grant period, the seven research groups that comprised the Genetic Toxicology Research Core during that period, published over 80 papers. Among other things they reported the following: N-acetylation phenotype strongly affects the toxicity and adduct levels of aromatic amines; the phosphorylation of the human ss-DNA binding protein (RPA) in response to ionizing radiation is defective in Ataxia Telangiectasia cells; cell cycle check points appear to behave differently in melanocytes from light-skinned populations compared with those from Native American and African-American people. A recent interest is the identification of genes responsible for genetic instability syndromes that predispose to cancer, such as Blooms Syndrome and Ataxia Telangiectasia. Future plans include increasing collaborative efforts, particularly in elucidating the function of the BLM gene product and the signaling pathway defects in Ataxia telangiectasia; developing systems for biomonitoring using human genes in transgenic mice; determining the relationship between specific DNA adducts and mutations in ras and p53 genes in the target tissues; and studying the effects of alpha-MSH on G1 arrest in melanocytes.
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