VALIDATION OF AN IN VITRO ASSAY FOR ANDROGENIC ACTIVITY

雄激素活性体外测定的验证

• 批准号: 9213081
• 负责人: Cathy Z Yang
• 金额: $ 57.6万
• 依托单位: CERTICHEM, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9213081
• 关键词: Adolescent; Adverse effects; Agonist; Androgen Receptor; Androgens; Attention; Autoimmune Diseases; Behavioral; Biological Assay; Brain; Breast Cancer Cell; Budgets; Cell Line; Cell Proliferation; Cells; Chemicals; Code; Collaborations; Complex Mixtures; Consultations; Cosmetics; Data; Development; Disease; Electronic Mail; Emotions; Endocrine Disruptors; Environment; Estrogens; Evaluation; Exhibits; Food Additives; Genetic Transcription; Glucocorticoid Receptor; Government Agencies; Grant; Health; Hormonal; Hormones; Human; Human Cell Line; Immune System Diseases; In Vitro; Incidence; Infant; Interagency Coordinating Committee on the Validation of Alternative Methods; Investigation; Laboratories; Learning Disabilities; Letters; Life; Luciferases; MCF7 cell; Malignant Neoplasms; Mammals; Manuals; Meta-Analysis; Methods; Mission; National Institute of Environmental Health Sciences; Neurodegenerative Disorders; Obesity; Ovarian Diseases; Paper; Pesticides; Pharmacologic Substance; Phase; Physiological Processes; Prevalence; Protocols documentation; Publishing; Reporter Genes; Reporting; Research; Robotics; Silicones; Small Business Innovation Research Grant; Sperm Count Procedure; Testing; Transcriptional Activation; United States Environmental Protection Agency; United States National Institutes of Health; Uterine Diseases; Validation; Writing; Xenobiotics; androgenic; base; cognitive development; consumer product; cost effective; dosage; estrogenic activity; fetal; high throughput screening; in vitro Assay; male; meetings; nanomolar; programs; reproductive; reproductive organ; screening; validation studies

 DESCRIPTION (provided by applicant): Recent scientific investigations have shown that many chemicals used in plastics, pharmaceuticals, pesticides, cosmetics, food additives, etc., are endocrine disrupting chemicals (EDCs). EDCs interfere in various ways with hormones, such as estrogens and androgens, and can have significant adverse effects on many behavioral and physiological processes. ED effects (agonistic or antagonistic) sometimes occur at very low (picomolar to nanomolar) concentrations, especially in fetal or developing mammals (including humans). The prevalence and actions of EDCs in our environment warrant the development of valid testing 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 EDCs, such as for androgenic (AnA) or anti- androgenic (Anti-AnA) activity. However, no reliable manual or robotic AnA or Anti-AnA assays are yet commercially available. ICCVAM/NICEATM desire single laboratory validation assays of AnA and Anti-AnA using a human-based cell line. To begin to meet these governmental, scientific and commercial needs, CertiChem (CCi) is submitting a Fast-Track grant to show that it is feasible to develop AnA and Anti-AnA assays in manual and medium- throughput (robotic) formats that would be reliable, accurate, versatile, rapid, and cost effective. CCi proposes to use MDA-kb2 human-based cells. In our AnA and anti-AnA assays, these cells will be examined by a transcription reporter gene (luciferase) assay. CCi proposes to examine 77 Test Substances supplied and coded by ICCVAM for AnA and Anti-AnA validation to confirm that CCi's assays can accurately assess their AR agonistic and antagonistic activities. CCi also proposes to test hydrophilic and hydrophobic extracts of 30 silicone and paper products for AnA and Anti-AnA. Development of manual and robotic screening assays for AnA and anti-AnA is highly desired as part of the mission of NIEHS, EPA, and ICCVAM as commercially, scientificly, and socially important. Government agencies are now screening a large number of chemicals for hormonal activity, including AR agonist and antagonist activities. In addition, hormonal activity of chemical mixtures extracted from commercial products is of great importance to government agencies, NGOs, and consumers.

 描述（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化学品（EDC）。 EDC 以多种方式干扰激素，例如雌激素和雄激素，并对许多行为和生理过程产生显着的不利影响。 ED 效应（激动性或拮抗性）有时会在非常低的浓度（皮摩尔至纳摩尔）下发生，特别是在胎儿或发育中的哺乳动物（包括人类）中。 EDC 在我们的环境中的普遍存在和作用需要开发有效的测试方法。因此，各个政府机构（例如 EPA、FDA 和 ICCVAM）和积极主动的公司明确表示希望对 EDC 进行体外机器人检测，例如雄激素 (AnA) 或抗雄激素 (Anti-AnA) 活性。然而，目前还没有可靠的手动或机器人 AnA 或抗 AnA 测定法在商业上可用。 ICCVAM/NICEATM 希望使用人类细胞系对 AnA 和抗 AnA 进行单一实验室验证测定。为了开始满足这些政府、科学和商业需求，CertiChem (CCi) 正在提交快速通道资助，以证明以手动和中等通量（机器人）形式开发 AnA 和抗 AnA 检测是可行的，这些检测可靠、准确、通用、快速且具有成本效益。 CCi 建议使用 MDA-kb2 人类细胞。在我们的 AnA 和抗 AnA 测定中，将通过转录报告基因（荧光素酶）测定来检查这些细胞。 CCi 建议检查由 ICCVAM 提供和编码的 77 种测试物质，用于 AnA 和抗 AnA 验证，以确认 CCi 的检测可以准确评估其 AR 激动和拮抗活性。 CCi 还建议测试 30 种有机硅和纸制品的亲水性和疏水性提取物中的 AnA 和 Anti-AnA。作为 NIEHS、EPA 和 ICCVAM 使命的一部分，非常需要开发 AnA 和抗 AnA 的手动和机器人筛选测定法，因为它具有商业、科学和社会重要性。政府机构现在正在筛选大量化学物质的激素活性，包括 AR 激动剂和拮抗剂活性。此外，从商业产品中提取的化学混合物的激素活性对于政府机构、非政府组织和消费者来说非常重要。