VALIDATION OF AN IN VITRO ASSAY FOR ANDROGENIC ACTIVITY

雄激素活性体外测定的验证

• 批准号: 9049209
• 负责人: Cathy Z Yang
• 金额: $ 19.28万
• 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: 2016-02-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9049209
• 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（由申请人提供）：最近的科学调查表明，许多用于塑料、药品、农药、化妆品、食品添加剂等的化学品，内分泌干扰物（EDCs）。内分泌干扰物以各种方式干扰激素，如雌激素和雄激素，并可能对许多行为和生理过程产生显着的不利影响。艾德效应（激动或拮抗）有时在极低浓度（皮摩尔至纳摩尔）下发生，尤其是在胎儿或发育中的哺乳动物（包括人类）中。内分泌干扰物在我们环境中的流行和作用保证了有效测试方法的发展。因此，各种政府机构（例如，EPA、FDA和ICCVAM）和积极的公司已经明确表达了对EDC进行体外机器人测定的愿望，例如雄激素（AnA）或抗雄激素（Anti-AnA）活性。然而，还没有可靠的手动或机器人AnA或抗AnA测定可商购获得。ICCVAM/NICEATM希望使用人源细胞系进行AnA和抗AnA的单一实验室验证试验。为了开始满足这些政府、科学和商业需求，CertiChem（CCi）正在提交一项快速通道资助，以证明以手动和中等通量（机器人）形式开发AnA和抗AnA检测试剂盒是可行的，这些检测试剂盒将是可靠的、准确的、通用的、快速的和具有成本效益的。CCi建议使用MDA-kb 2人类细胞。在我们的AnA和抗AnA试验中，这些细胞将通过转录报告基因（荧光素酶）试验进行检查。CCi建议检查由ICCVAM提供和编码的77种供试品，以进行AnA和抗AnA验证，以确认CCi的检测方法可以准确评估其AR激动和拮抗活性。CCi还建议对30种硅胶和纸制品的亲水性和疏水性浸提液进行AnA和抗AnA检测。作为NIEHS、EPA和ICCVAM的使命的一部分，高度期望开发AnA和抗AnA的手动和机器人筛选测定，因为其在商业上、科学上和社会上是重要的。政府机构目前正在筛选大量化学品的激素活性，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政府机构，非政府组织和消费者非常重要。