Variable Dose Rate X-ray Irradiator

说明(申请人提供)：电离辐射在治疗人类癌症中发挥着重要作用，而暴露在相对较低剂量下可导致癌症、致畸和突变后果。哥伦比亚大学的实验室研究探索了辐射引起的变化的细胞、生化和分子基础，希望在生物、组织、细胞和亚细胞水平上阐明所造成的损害的类型和影响的反应。此外，电离辐射已成为促进我们NIH资助的研究的常见工具，即使定义对辐射的生物反应本身并不是该研究的主要目标。在这份提案中，我们要求考虑购买X-RAD 320生物辐射器所需的资金，这是一种可变剂量率X射线发射器。研究人员将利用X光机在分子水平上研究从辐射诱导的DNA损伤修复到动脉粥样硬化、癌症、白内障发生和神经发育的方方面面。可用的剂量率范围和交付的精确度是对各种模型系统进行研究的理想选择，例如抗辐射酵母、黑腹果蝇和秀丽线虫，以及培养中的哺乳动物细胞或小型啮齿动物。Rothstein和Symington博士将研究酵母中DNA修复和复制的机制。约翰斯顿博士将利用果蝇作为组织损伤修复的模型，通过涉及增殖和再生的机制进行修复。霍伯特博士将利用秀丽隐杆线虫研究神经发生，而亨博士将利用小鼠研究海马体发育。费尔斯坦博士将使用同样的模型生物体来研究嗅觉系统。迪亚科沃博士将研究小鼠的关节炎，塔巴斯博士将研究这些小型啮齿动物的动脉粥样硬化。贝尔、布鲁斯、黑和利伯曼博士的研究小组将使用人类和小鼠细胞和/或整个小鼠在基本分子水平上检查辐射的分子反应，特别是与脑癌、乳腺癌、卵巢癌和/或前列腺癌以及白内障形成有关的分子反应。因此，X-RAD 320将被哥伦比亚大学的研究人员广泛使用，以解决利用X辐射进行的一大批重要的生物医学研究领域。这些设备将并入赫伯特·欧文综合癌症中心辐射研究核心设施目前完善的基础设施中，并由其进行维护，该中心位于哥伦比亚大学医学中心放射研究中心内，并由该中心赞助。

DESCRIPTION (provided by applicant): 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.