ANALYZING TOXICITY TO MAMMALIAN CELLS BY FLOW CYTOMETRY

通过流式细胞术分析对哺乳动物细胞的毒性

• 批准号: 2545794
• 负责人: DOROTHEA K TOROUS
• 金额: $ 23.08万
• 依托单位: LITRON LABORATORIES, LTD.
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 1998-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2545794
• 关键词: carcinogen testing; cytotoxicity; erythrocytes; flow cytometry; gene mutation; laboratory mouse; method development; micronucleus; mutagen testing; thymidine kinase; tissue /cell culture; tumor promoters

Chemicals play an important role int he quality of life in the modern world, and industrial laboratories are continuously developing new chemical formulations for a myriad of applications. It is important to characterize the inherent toxicity of new chemicals so that agents harmful to the populace can be identified. This research program is designed to both enhance the predictive power and reliability of chemical toxicity assays, and to reduce the number of animals required for testing. Many years of research strongly suggest that high-speed flow cytometry (FCM) is a technology which can significantly improve toxicity tests. With FCM, cells are moved at high speeds through a focused laser beam. Cell associated signals corresponding to particle size and fluorescent signals are stored to computer file for later analysis. Modern flow cytometers are capable of analyzing cells at extremely high rates (10,000 cells/sec). Once biological, chemical and FCM parameters are optimized, FCM technology is able to provide the following scoring characteristics: objectivity, efficiency, high throughput, and unprecedented accuracy. Advanced technologies such as FCM therefore have a great potential to significantly improve toxicity assays by permitting more expeditious and reliable analyses of biological responses to chemical exposure. The major research objectives of this application specifically relate tot he automation of three important mammalian toxicity endpoints: chromosome damaging effects, tumor promotion, and gene mutation. The experiments proposed for Phase II are intended to further develop and validate these automated test systems, and establish Litron Laboratories as an expert testing facility which is capable of providing industry and government with highly reliable FCM-based toxicity tests. A significant market exists for a facility which can supply such automated and improved assays. PROPOSED COMMERCIAL APPLICATION: ...New methods are needed to advance toxicology testing which can reduce the use of animals and moderate testing costs. ...Flow cytometry provides technology that expedites testing by objectively analyzing cell populations at high speeds. ...The commercial application of the technology is for reaching to industries that develop chemicals and pharmaceuticals where testing is required prior to broad distribution.

化学品在现代生活质量中起着重要作用 世界，工业实验室正在不断开发新的化学品 用于无数应用的配方。 重要的是， 新化学品的固有毒性， 群众可以识别。 这项研究计划旨在 增强化学毒性测定的预测能力和可靠性， 并减少测试所需的动物数量。 多年的研究强烈表明，高速流式细胞术 (FCM)是一项可以显著改善毒性测试的技术。 与 FCM，细胞通过聚焦激光束高速移动。 细胞 对应于颗粒尺寸和荧光信号的相关信号 储存在电脑档案中供日后分析。 现代流式细胞仪 能够以极高的速率（10，000个细胞/秒）分析细胞。 一旦生物、化学和FCM参数被优化， 能够提供以下评分特征：客观性， 高效率、高吞吐量和前所未有的准确性。 先进 因此，FCM等技术具有巨大的潜力， 通过允许更迅速和可靠的毒性测定来改进毒性测定 分析化学品暴露的生物反应。 本申请的主要研究目标具体涉及： 三个重要哺乳动物毒性终点的自动化：染色体 破坏作用、肿瘤促进和基因突变。 实验 为第二阶段提出的建议旨在进一步发展和验证这些 自动化测试系统，并建立Litron实验室作为专家 测试设施，能够为工业和政府提供 高度可靠的基于FCM的毒性测试。 一个重要的市场存在， 一种可以提供这种自动化和改进的化验的设备。 建议的商业应用：.需要新的方法来推进 毒理学测试，可以减少使用动物和适度的测试 成本 ...流式细胞术提供了通过以下方式加速检测的技术： 以高速客观地分析细胞群体。 ...商业 技术的应用是为了达到发展中的行业， 化学品和药品，在广泛使用之前需要进行测试 分布