X-irradiator for in vivo and in vitro studies with relevance to basic stress sign

描述（由申请人提供）：本申请用于购买一台独立的X光机，该X光机将用于伦巴第综合癌症中心（LCCC）的放射生物学项目，并将成为LCCC成员以及乔治敦大学其他研究人员的核心资源。该XRAD 320由Precision X-RAY Inc.制造。(PXI)，这一领域的领导者。目前，LCCC每年从NCI获得的直接费用为2850万美元，同行评审的资金每年直接费用超过5300万美元，放射生物学计划（MTTR）有900万美元;其中大部分是NIH的资金。虽然许多研究项目和调查人员依赖于可靠的电离辐射源（IR），但唯一可供30多名用户使用的设备是137 Cs源伽马辐照器 *，该设备是15年前由NIH仪器拨款购买的。虽然它是一个有用的仪器，用于许多应用，37 Cs源γ辐照器有各种重要的限制，包括一个小的字段大小（小于XRAD 320的一半，均匀性较差），剂量率的范围不足的一些低剂量率实验，和温度和CO2气体控制能力不足的长期组织培养研究。目前，小场地甚至阻止使用中等大小的实验室动物，如成年兔，以及使用小动物，如小鼠的长时间实验，其中需要合理大小的笼具和水和食物。在动物肿瘤模型中进行局部照射和局部实验放射治疗通常只能使用XRAD 320提供的聚焦光束进行，而不是当前的辐照器。此外，如同位素医疗用途咨询委员会报告（NRC 2008-0184）中详细讨论的，同位素源辐照器存在重大安全问题，本报告中概述的长期解决方案是用X辐照器取代同位素辐照器，例如NRC 2008-0184中提到的PXI辐照器。我们目前的政策，以解决安全问题，是密切监测所有访问和辐射大大增加了环境健康与安全办公室的人员成本。运营成本也更低，因为没有重新装载或退役费用，加上设备每年只需要低成本的预防性维护访问。如本申请中其他地方所述，XRAD 320将允许进行各种实验，这些实验在当前设备上不实用或不可行，并且目前由NIH和其他政府资金支持。XRAD 320将扩大NIAID支持的研究的范围并使其受益，这些研究与辐射事故或恐怖主义的监测和响应直接相关。它将有利于各种NCI支持的肿瘤细胞辐射敏感性机制的研究，以及NIEHS支持的基础和应用研究，以开发各种毒理学暴露的生物标志物。* 由于NRC对伽马辐照器的安全要求，本申请中未提供当前伽马辐照器的制造商、型号、序列号和总放射性。

DESCRIPTION (provided by applicant): This application is for the purchase of a self-contained x-ray machine that will be based in the radiobiology program of the Lombardi Comprehensive Cancer Center (LCCC) and that will be a core resource for members of the LCCC as well as for other researchers at Georgetown Univ. The unit, the XRAD320, is manufactured by Precision X-RAY Inc. (PXI), a leader in this field. Currently, the LCCC has $28.5 million in annual direct costs from NCI and peer-reviewed funding annual direct costs exceed $53 million, and the radiobiology program (MTTR) has $9 million; the majority of this is NIH funding. While numerous research projects and investigators depend on a reliable source for ionizing radiation (IR), the only available unit for over 30 users is a 137Cs source gamma-irradiator* which was purchased with a NIH instrumentation grant 15 years ago. Although it is a useful instrument for many applications, the 37Cs source gamma-irradiator has a variety of important limitations including a small field size (<half of XRAD320 with less uniformity), an insufficient range of dose-rates for some low dose rate experiments, and inadequate capability for temperature and CO2 gas control for prolonged tissue culture studies. Currently, the small field prevents the use of even moderate size laboratory animals, such as adult rabbits, and prolonged experiments with small animals, such as mice, where a reasonable size cage with water and chow is required. Partial body irradiation and localized experimental radiotherapy in animal tumor models can usually only be carried out with a focused beam which can be provided by the XRAD320 and not the current irradiator. In addition, there is a major security concern for isotope source irradiators as discussed in detail in the Advisory Committee on the Medical Uses of Isotopes's Report (NRC 2008-0184), and the long term solution, as outlined in this report, is to replace isotope irradiators with x-irradiators, such as those from PXI which was mentioned in NRC 2008-0184. Our current policy to address security concerns, are to closely monitor all access and irradiation substantially increasing personnel costs for the Office of Environmental Health & Safety. Operating costs are also lower because there are no reloading or decommissioning expenses, plus the equipment requires only a low cost preventative maintenance visit annually. As outlined elsewhere in this application, the XRAD320 will allow for a variety of experiments that are not practical or feasible with the current unit, and that are currently supported by NIH as well as other government funding. The XRAD320 will expand the scope and benefit NIAID-supported studies which are directly relevant to monitoring and responses to radiologic accidents or terrorism. It will benefit a variety of NCI-supported studies into mechanisms of radiation sensitivity of tumor cells, and basic and applied studies supported by NIEHS to develop biomarkers for various types of toxicological exposures. * Due to NRC security requirements for gamma irradiators, the manufacturer, model number, serial number, and total activity of the current gamma irradiator is withheld from this application..