An In Vitro Robotic Assay for Anti-Estrogenic Activity

抗雌激素活性的体外机器人测定

• 批准号: 7109578
• 负责人: Cathy Z Yang
• 金额: $ 12.18万
• 依托单位: CERTICHEM, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7109578
• 关键词: MCF7 cell; bioengineering /biomedical engineering; biohazard detection; cell proliferation; endocrine disrupting compound; environmental toxicology; estrogen inhibitor; flavones; flavonoids; genistein; high performance liquid chromatography; lactones; phytoestrogens; progesterone; robotics; tamoxifen; technology /technique development

DESCRIPTION (provided by applicant): Recent scientific investigations have shown that many chemicals used in plastics, Pharmaceuticals, pesticides, cosmetics, food additives, etc., are endocrine disrupters (EDs). EDs interfere in various ways with hormones such as estrogens to have significant adverse effects on many behavioral and physiological processes. ED effects (e.g. estrogenic or anti-estrogenic) sometimes occur at very low (picomolar to nanomolar) concentrations, especially on fetal or developing mammals (including humans). The prevalence and actions of EDs in our environment warrant the development of valid assay methods. Consequently, various governmental bodies (e.g., EPA, FDA, and ICCVAM) and proactive corporations have explicitly expressed a desire to have in vitro robotic assays for EDs, such as anti-estrogenic activity (anti-EA). However, no anti-EA assay is commercially available. To begin to meet these governmental, scientific and commercial needs, CertiChem (CCi) has preliminary data suggesting that it is feasible to develop an anti-EA robotic assay that would be valid (i.e., reliable, accurate, versatile, rapid, and cost effective) using MCF-7 cells. In this Phase I application, CCi now proposes to confirm that it is feasible to develop a robotic assay for anti-EA by first determining an optimum robotic protocol for detecting anti-EA using MCF-7 cells. CCi then proposes to estimate the reliability (reproducibility) of this assay by repeatedly (5 times) assaying over a 12 week period a limited set of reference chemicals (10) published by ICCVAM to use for validation of anti-EA assays (Specific Aim #1). CCi also proposes (Specific Aim #2) to estimate the accuracy of this assay by comparing data CCi obtains on these 10 reference chemicals with data published by ICCVAM. We strongly expect data obtained on this Phase I grant to confirm our preliminary data that this anti-EA assay is worthy of more extensive testing and development in a Phase II study to prepare it for commercialization. Development of a robotic screening assay for anti-EA is commercially, scientifically, and socially important because of the large number of chemicals (>10,000) - much less chemical mixtures - that should now be screened for anti-EA by profit, non-profit, or governmental entities. Development of a robotic assay for anti-EA is desired as part of the mission of NIEHS, EPA and ICCVAM.

描述（由申请人提供）：最近的科学研究表明，塑料、药品、农药、化妆品、食品添加剂等中使用的许多化学品都是内分泌干扰物（ED）。 ED 以多种方式干扰雌激素等激素，对许多行为和生理过程产生显着的不利影响。 ED 效应（例如雌激素或抗雌激素）有时会在非常低的浓度（皮摩尔至纳摩尔）下发生，特别是对胎儿或发育中的哺乳动物（包括人类）。我们环境中 ED 的流行和作用需要开发有效的检测方法。因此，各个政府机构（例如 EPA、FDA 和 ICCVAM）和积极主动的企业已明确表达了对 ED 进行体外机器人检测的愿望，例如抗雌激素活性（抗 EA）。然而，目前还没有商业化的抗 EA 检测方法。为了开始满足这些政府、科学和商业需求，CertiChem (CCi) 的初步数据表明，开发一种有效的抗 EA 机器人检测是可行的（即可靠、准确、通用、快速且具有成本效益） ）使用 MCF-7 细胞。在此一期应用中，CCi 现在建议通过首先确定使用 MCF-7 细胞检测抗 EA 的最佳机器人方案来确认开发抗 EA 机器人检测是可行的。然后，CCi 建议通过在 12 周内重复（5 次）测定 ICCVAM 发布的一组有限的参考化学品 (10) 来估计该测定的可靠性（再现性），以用于验证抗 EA 测定（具体目标 # 1). CCi 还建议（具体目标 #2）通过将 CCi 获得的这 10 种参考化学品的数据与 ICCVAM 发布的数据进行比较来估计该测定的准确性。我们强烈期望第一阶段资助获得的数据能够证实我们的初步数据，即这种抗 EA 测定值得在第二阶段研究中进行更广泛的测试和开发，为商业化做好准备。开发抗 EA 机器人筛选试验具有商业、科学和社会重要意义，因为大量化学品 (>10,000)（更不用说化学混合物）现在应该由营利性、非营利性组织进行抗 EA 筛选或政府实体。作为 NIEHS、EPA 和 ICCVAM 使命的一部分，需要开发一种抗 EA 机器人检测方法。