Ionizing radiation plays a significant role in the treatment of human cancers, while exposure to relatively low doses can lead to the induction of cancer, to teratogenesis and 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 type of damage incurred and the responses in effect at the level of the organism, the tissue, the cell, and at the subcellular level. Furthermore, ionizing radiation has become a common tool to facilitate our NIH-funded investigations even when defining the biological response to radiation, per se, is not the primary goal of the study. In this proposal, we request consideration for the funds needed to purchase a X-RAD 320 Biological Irradiator, a variable dose rate x-ray emitter. Investigators will make use of the x-ray machine to study everything from radiation-induced DNA damage repair at the molecular level to atherosclerosis, carcinogenesis, cataractogenesis, and neurological development. The range of dose rates available and the precision with which delivery can be made are ideal to enable studies to be undertaken on a wide array of model systems such as radioresistant yeast, Drosophila melanogaster and Caenorhabditis elegans, as well as mammalian cells in culture, or small rodents. Drs. Rothstein and Symington would study mechanisms of DNA repair and replication in yeast. Dr. Johnston would use Drosophila as a model of tissue damage repair through mechanisms involving proliferation and regeneration. Caenorhabditis elegans will be used by Dr. Hobert to study neurogenesis, while Dr. Hen will employ mice to study hippocampal development. Dr. Firestein will use the same model organism to investigate the olfactory system. Dr. Diacovo will study arthritis in mice, and Dr. Tabas will investigate atherosclerosis in these small rodents. Drs. Baer, Bruce, Hei and Lieberman have research groups that will use human and mouse cells and/or whole mice to examine the molecular response to radiation at a rudimentary molecular level, as well as specifically in relation to cancer of the brain, breast, ovary and/or prostate, and cataract formation. The X-RAD 320 will therefore be widely used by investigators from Columbia University addressing a large array of important biomedical areas of research that make use of x-irradiation. The equipment would fold into and be maintained by the current, well-established infrastructure of the Radiation Research Core Facility of the Herbert Irving Comprehensive Cancer Center, which is located within and falls under the auspices of the Center for Radiological Research at the Columbia University Medical Center.
