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

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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..