Ionizing radiation play a significant role in the treatment of human cancers, while exposure to relatively low doses can lead to the induction of cancer, to teratogenic and to mutagenic consequences. Laboratory studies at Columbia University have explored the cellular , biochemical, and molecular bases for radiation-induced change in the hope of elucidating the types of damage incurred and the responses in effect at the level of the organism, the tissue, the cell, and at the subcellular level. In this proposal, we request consideration for receipt of the funds needed to purchase a Gammacell 220, a high-dose-rate gamma-ray emitter. This will enable studies to be undertaken on small animals, on mammalian cells in culture, on radioresistant eukaryotes such as Drosophila and yeast, and on prokaryotes and macromolecules where exposure time is now prohibitive using presently available equipment. Dr. Rothstein would study the biological role of recombination in yeast after irradiation, and studies in Dr. Lieberman's laboratory would focus on the molecular characterization of DNA repair in yeast and human systems. Dr. Worgul will be able to study optical tissue damage in large numbers of rodents and amphibians, with a reduction in the initial trauma to the test organisms. Again to study large numbers of animals and with less trauma, Dr. Bank will use the machine to irradiate mice for studies involving bone marrow transplantation and optimization of a gene therapy protocol. Dr. Erlanger will irradiate purified DNA, as well as mammalian cells in culture, with very high doses of gamma rays to induce DNA damage that will be used for the preparation of lesion-specific monoclonal antibodies. Other users would be able to examine and potentially modulate immediately after irradiation a variety of endpoints expressed in cells, especially since the delivery time for even high doses would be negligible in comparison to the times needed for expression of the cellular responses to irradiation that would be monitored. These parameters would include repair phenomena affecting mammalian cell survival (Drs. Astor and Hall), induction of chromosomal abnormalities (Dr. Geard), mutagenesis (Dr. Hei), and focus formation as an indication of transformation (Dr. Miller).
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