This application is to improve my research and training capability by collaborating with an established scientist at the NASA Space Flight Center, Huntsville, which is one of the major research installations in the U.S. This will be achieved by researching for five successive summers at the NASA center. The research will involve experiments Ataxia cell lines. The cytogenetic features of Ataxia telangiectasia include spontaneous chromosomal instability, clonal occurrence of rearrangements involving in particular, chromosome 7 and 14, chromosomal and cellular hypersensitivity to ionizing radiation, radio-resistant DNA synthesis, deficient DNA repair and cancer proneness. In 1995, the AT gene was mapped to the long arm of chromosome region 11q 22-23. In A-T patients, the increased radio- sensitivity to ionizing radiation is seen as increased chromosome aberrations, cell killing and a high risk for developing lymphomas and lymphatic leukemias. A-T heterozygotes are phenotypically normal but are at a higher risk of developing breast cancer; carrier woman have a five-fold risk for breast cancer over that of normal woman. Despite extensive biochemical investigations the molecular defect for the increased radio- sensitivity in AT remains unexplained. We will perform experiments to understand how the primary damage to DNA induced by radiation becomes expressed as chromosomal aberrations and how the unrepaired damage generates cancer prone cells by initiating a process of genetic instability. The research involves several new techniques which will be acquired during the summer and used during the following academic year at the Alabama A&M University. During the academic year graduate and undergraduate students will participate in the research and receive research experience and training.
