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

描述（由申请人提供）：本申请是为了购买一台独立的x光机，该x光机将基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。该设备名为XRAD320，由精密x射线公司（PXI）制造，该公司是该领域的领导者。目前，LCCC每年从NCI和同行评审基金获得2850万美元的直接费用，每年直接费用超过5300万美元，放射生物学项目（MTTR）获得900万美元；其中大部分是NIH资助的。虽然许多研究项目和研究人员依赖于可靠的电离辐射源（IR），但30多个用户唯一可用的单位是15年前用NIH仪器补助金购买的137Cs源γ辐照器*。虽然37Cs源γ辐照器在许多应用中是一种有用的仪器，但它有各种重要的局限性，包括小的场尺寸（< XRAD320的一半，均匀性较差），一些低剂量率实验的剂量率范围不足，以及对长时间组织培养研究的温度和CO2气体控制能力不足。目前，由于场地狭小，即使是中等大小的实验动物（如成年兔子）也无法使用，而且小动物（如小鼠）也无法进行长时间的实验，因此需要一个大小合理的装有水和食物的笼子。在动物肿瘤模型中，局部体照射和局部实验放疗通常只能通过XRAD320提供的聚焦光束进行，而目前的辐照器无法提供。此外，同位素医学用途咨询委员会报告（NRC 2008-0184）详细讨论了同位素源辐照器的主要安全问题，该报告概述的长期解决办法是用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。我们目前解决安全问题的政策是密切监测所有进出和辐照，这大大增加了环境健康与安全办公室的人员成本。运营成本也较低，因为没有重新装填或退役费用，而且设备每年只需要进行一次低成本的预防性维护访问。正如本应用程序中其他地方概述的那样，XRAD320将允许各种实验，这些实验在当前单元中是不实际或不可行的，并且目前由NIH以及其他政府资助。XRAD320将扩大范围并使niaid支持的研究受益，这些研究与辐射事故或恐怖主义的监测和反应直接相关。它将有利于nci支持的肿瘤细胞辐射敏感性机制的各种研究，以及NIEHS支持的基础和应用研究，以开发各种类型毒理学暴露的生物标志物。*由于NRC对伽玛辐照器的安全要求，制造商，型号，序列号和当前伽玛辐照器的总活动在本申请中被保留。

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..