FLOW CYTOMETRIC RAT MICRONUCLEUS ASSAY

流式细胞术大鼠微核测定

• 批准号: 6140038
• 负责人: DOROTHEA K TOROUS
• 金额: $ 37.78万
• 依托单位: LITRON LABORATORIES, LTD.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2002-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6140038
• 关键词: DNA damage; bioassay; biomedical automation; blood tests; bone marrow; cytotoxicity; flow cytometry; laboratory rat; method development; micronucleus; stainings; toxicant screening; toxin

Chemicals play an important role in our quality of life, thus it is important to characterize the toxicity of new chemicals so that harmful agents can be highlighted prior to public exposure. The micronucleus (MN) assay is the most widely used system or evaluating a chemical's potential to cause chromosomal damage. This research project will broaden the database of genotoxins analyzed by flow cytometry (FCM), assessing whether rat peripheral blood (after acute or subchronic treatment) is an appropriate compartment for detecting damage caused by genotoxic compounds. Since rat bone marrow is currently accepted by regulatory agencies worldwide, a major line of investigation is to further develop reliable methods for preparing bone marrow samples for FCM analysis. A significant in te rest for automating the rat peripheral blood assay is that the spleen of this species behaves similarly to that of humans. Therefore, this work is extremely important towards our long-term goal of analyzing human blood for the presence of MN. When we are able to measure MN in human blood, it might be possible to determine the genotoxic effects of accidental human exposure and even biomonitor patients receiving chemotherapeutic treatments. PROPOSED COMMERCIAL APPLICATION: Litron, together with the Stratagene Corporation, is developing micronucleus kits for rat peripheral blood and bone marrow. The kits will be in two formats: the first allows researchers to send blood samples to Litron for MN analysis (microFlow kits)to analyze for MN, and the second allows researchers to analyze for MN in-house (micro FlowPlus kits). The pharmaceutical community has responded enthusiastically and has asked for the development of rat kits specifically for their in-house use in addition to the kits, we expect our genetic toxicology contract testing to increase as this advanced technology is refined and brought to the marketplace.

化学品在我们的生活质量中发挥着重要作用，因此表征新化学品的毒性非常重要，以便在公众接触之前突出显示有害物质。微核 (MN) 测定是最广泛使用的系统，用于评估化学物质造成染色体损伤的可能性。该研究项目将扩大流式细胞术（FCM）分析的基因毒素数据库，评估大鼠外周血（急性或亚慢性治疗后）是否适合检测基因毒性化合物造成的损伤。由于大鼠骨髓目前已被世界各地的监管机构所接受，因此主要的研究方向是进一步开发可靠的方法来制备用于 FCM 分析的骨髓样本。自动化大鼠外周血测定的一个重要意义是该物种的脾脏的行为与人类相似。因此，这项工作对于我们分析人类血液中是否存在 MN 的长期目标极其重要。当我们能够测量人类血液中的微核时，就有可能确定人类意外暴露甚至接受化疗的生物监测患者的基因毒性影响。拟议的商业应用：Litron 与 Stratagene Corporation 正在开发用于大鼠外周血和骨髓的微核试剂盒。该试剂盒将有两种形式：第一种允许研究人员将血液样本发送到 Litron 进行 MN 分析（microFlow 试剂盒）来分析 MN，第二种允许研究人员在内部分析 MN（micro FlowPlus 试剂盒）。制药界反应热烈，除了试剂盒外，还要求开发专门供其内部使用的大鼠试剂盒，随着这项先进技术的完善并推向市场，我们预计我们的遗传毒理学合同测试将会增加。