Variable Dose Rate X-ray Irradiator

描述（由申请人提供）：电离辐射在人类癌症的治疗中起着重要作用，而暴露于相对低剂量的电离辐射可导致癌症的诱发、致畸和诱变后果。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，希望能阐明在生物体、组织、细胞和亚细胞水平上发生的损伤类型和反应。此外，电离辐射已经成为促进我们美国国立卫生研究院资助的研究的常用工具，即使定义辐射的生物反应本身并不是研究的主要目标。在本提案中，我们要求考虑购买X-RAD 320生物辐照器所需的资金，这是一种可变剂量率的x射线发射器。研究人员将利用x光机来研究从分子水平上辐射诱导的DNA损伤修复到动脉粥样硬化、癌症发生、白内障发生和神经发育的一切。可用的剂量率范围和精确的递送是理想的，可以在广泛的模型系统上进行研究，如耐辐射酵母、黑腹果蝇和秀丽隐杆线虫，以及培养中的哺乳动物细胞或小型啮齿动物。Drs。罗斯坦和辛明顿将研究酵母DNA修复和复制的机制。约翰斯顿博士将果蝇作为通过增殖和再生机制修复组织损伤的模型。霍伯特博士将使用秀丽隐杆线虫来研究神经发生，而亨博士将使用小鼠来研究海马发育。费尔斯坦博士将使用同样的模型生物来研究嗅觉系统。Diacovo博士将研究小鼠的关节炎，Tabas博士将研究这些小型啮齿动物的动脉粥样硬化。Drs。Baer, Bruce， Hei和Lieberman的研究小组将使用人类和小鼠细胞和/或整只小鼠在基本分子水平上检查对辐射的分子反应，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的关系。因此，X-RAD 320将被哥伦比亚大学的研究人员广泛应用于利用x射线照射的大量重要生物医学研究领域。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的现有基础设施，并由其维护，该中心位于哥伦比亚大学医学中心放射研究中心内，并受其主持。

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.