Rapid Screen for Genotoxicants, Chemoprotectors, and Radioprotectors

描述（由申请人提供）：这个研究项目解决了化学和药物工业面临的一个重要问题。他们需要在更短的时间内评估数量越来越多的新化学实体对DNA的破坏潜力。这种情况为能够为这些挑战提供解决方案的小型企业提供了机会。本文提出的工作通过开发一种自动化的体外染色体损伤试验，解决了工业界对高通量毒性评估的需求。染色体损伤将通过流式细胞仪微核测量来量化。重要的是，在这个项目的过程中，将开发的方法不仅代表了一个大容量的基因毒物筛选系统，而且还可以配置为识别防止染色体损伤的药物。该项目解决了研究人员开发下一代生物反应调节剂（BRMs）的既定需求。提供化学或放射保护的brm在几个重要领域具有很大的前景，包括通常受正常组织反应剂量限制的癌症治疗。brm的识别和发展还有其他重要的应用，包括在战争期间加强对我们部队的保护，以及对化学或放射性恐怖袭击的平民受害者的保护。因此，计划的1期和2期工作旨在提供一种快速有效的分析方法，用于检测测试化学品的基因毒性、放射性保护剂或化学保护剂潜力。这种筛选试验将帮助化学和药物公司将资源分配给最有希望的候选药物，在开发早期消除危险实体。此外，通过帮助识别下一代brm，癌症患者和武装部队将受益于化学和放射保护药物的可用性。

DESCRIPTION (provided by applicant): This research project addresses an important problem faced by the chemical and drug industries? their requirement to evaluate the DNA damaging potential of ever larger numbers of new chemical entities in shorter periods of time. This situation presents opportunities for small businesses that are able to provide solutions to these challenges. The work proposed herein addresses industry's need for higher throughput toxicity assessment through the development of an automated in vitro chromosomal damage assay. Chromosome damage will be quantified by flow cytometric micronucleus measurements. Importantly, the methodology that will be developed over the course of this project not only represents a high volume genotoxicant screening system, but also one that can be configured to identify agents which protect against chromosomal damage. This project addresses a stated need of investigators working to develop the next generation of biological response modifiers (BRMs). BRMs that provide chemo- or radio-protection hold great promise in several important arenas, including cancer treatments which are typically dose-limited by normal tissue responses. The identification and development of BRMs have other important applications, and include enhanced protection of our troops during times of war, and also for civilian victims of chemical or radiological terrorist attacks. The planned Phase 1 and Phase 2 efforts have thus been designed to provide a rapid and efficient assay for detecting the genotoxicant, radioprotectant, or chemoprotectant potential of test chemicals. This screening assay will help chemical and drug companies allocate their resources to the most promising candidates, eliminating hazardous entities early in development. Furthermore, by aiding in the identification of next generation BRMs, cancer patients and armed forces will benefit from the availability of chemo- and radio-protectant drugs.