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）：最近的科学调查表明，许多用于塑料、药物、农药、化妆品、食品添加剂等的化学品，内分泌干扰物（EDs）。ED以各种方式干扰激素，如雌激素，对许多行为和生理过程产生显着的不利影响。艾德效应（例如雌激素或抗雌激素）有时在非常低的浓度（皮摩尔至纳摩尔）下发生，尤其是对胎儿或发育中的哺乳动物（包括人类）。ED在我们环境中的流行和作用保证了有效的检测方法的发展。因此，各种政府机构（例如，EPA、FDA和ICCVAM）和积极主动的公司已经明确表达了对ED进行体外机器人测定的愿望，例如抗雌激素活性（抗EA）。然而，没有市售的抗EA测定。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机器人测定是可行的（即，可靠、准确、通用、快速和成本效益）。在该I期申请中，CCi现在提出通过首先确定使用MCF-7细胞检测抗EA的最佳机器人方案来确认开发抗EA的机器人测定是可行的。然后，CCi建议通过在12周内重复（5次）测定ICCVAM发布的用于验证抗EA测定（具体目标#1）的一组有限的参比化学品（10）来估计该测定的可靠性（重现性）。CCi还建议（具体目标#2）通过比较CCi获得的这10种参比化学品的数据与ICCVAM发布的数据来估计该测定的准确度。我们强烈期望在第一阶段获得的数据能够证实我们的初步数据，即这种抗EA检测方法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。开发用于抗EA的机器人筛选测定在商业上、科学上和社会上是重要的，因为大量的化学品（> 10，000）-更少的化学混合物-现在应该由营利、非营利或政府实体筛选抗EA。作为NIEHS、EPA和ICCVAM的使命的一部分，需要开发用于抗EA的机器人测定。