Rapid Screen for Genotoxicants, Chemoprotectors, and Radioprotectors

描述(申请人提供)：这项研究项目解决了化学和制药行业面临的一个重要问题？他们要求在更短的时间内评估越来越多的新化学实体的DNA损伤潜力。这种情况为能够为这些挑战提供解决方案的小企业提供了机会。本文提出的工作通过开发一种自动化的体外染色体损伤分析来满足行业对更高吞吐量毒性评估的需求。染色体损伤将通过流式细胞仪微核测量进行量化。重要的是，将在该项目过程中开发的方法不仅代表了一个大容量的遗传毒物筛选系统，而且还可以配置为识别保护免受染色体损害的制剂。该项目满足了致力于开发下一代生物反应调节剂(BRM)的研究人员的明确需求。提供化学或放射防护的BRMS在几个重要领域有着巨大的希望，包括癌症治疗，这些治疗通常受到正常组织反应的剂量限制。核生化武器的确定和发展还有其他重要用途，包括在战争期间加强对我们部队的保护，以及为化学或放射性恐怖袭击的平民受害者提供保护。因此，计划的第一阶段和第二阶段的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遗传毒性、辐射保护剂或化学保护剂的潜力。这种筛查试验将帮助化学和制药公司将他们的资源分配给最有希望的候选者，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疗和放射保护药物的可获得性。

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.