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（由适用提供）：最近的科学研究表明，塑料，药物，农药，化妆品，食物添加剂等用于内分泌干扰化学物质（EDC）的许多化学物质。 EDC以各种方式干扰辣根和雄激素，并可能对许多行为和物理过程产生重大不利影响。 ED效应（激动或拮抗）有时会出现在非常低的（皮摩尔至纳摩尔）浓度下，尤其是在胎儿或发育中的哺乳动物（包括人）中。 EDC在我们环境中的患病率和行动值得开发有效的测试方法。因此，各种政府机构（例如EPA，FDA和ICCVAM）和积极主动的公司明确表示希望对EDC进行体外机器人测定，例如雄激素（ANA）或抗雄激素（抗雄激素）活性。但是，尚无可靠的手册或机器人ANA或反对ANA分析。 ICCVAM/NICEATM DESSINE使用基于人类的细胞系对ANA和Antia ANA的单实验室验证测定法。为了开始满足这些政府，科学和商业需求，Certichem（CCI）正在提交快速拨款赠款，以表明以手动和中型和中型（机器人）格式开发ANA和反ANA测定法是可靠的，这些格式将是可靠，准确，准确，快速，快速，快速，快速和成本效益的。 CCI建议使用MDA-KB2基于人类的细胞。在我们的ANA和抗ANA测定中，这些细胞将通过转录报告基因（荧光素酶）测定法检查。 CCI提案审查ICCVAM提供和编码的77种测试物质，以确认CCI的测定方法可以准确评估其AR激动和拮抗活性。 CCI还建议测试30种有机硅和纸质产品的亲水和疏水提取物，用于ANA和抗ANA。作为商业，科学和社会上重要的NIEHS，EPA和ICCVAM的一部分，高度期望为ANA和Antia的手动筛选测定法开发。政府机构现在正在筛选大量用于马的化学物质，包括AR激动剂和对手活动。此外，从商业产品中提取的化学混合物的激素活性对政府机构，非政府组织和消费者至关重要。