Validation of Organotypic Vaginal Tissue Based Assay for Endocrine Disruptors

基于器官型阴道组织的内分泌干扰物测定的验证

基本信息

批准号：
7270190
负责人：
Seyoum Ayehunie
金额：
$ 21.18万
依托单位：
MATTEK CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-01 至 2009-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7270190
关键词：
Adrenocortical carcinoma Advisory Committees Affect Agonist Agriculture Androgens Animal Model Animal Testing Animals Anus Area Aromatase Aromatase Inhibition Biological Assay Brain CYP19A1 gene Cell Line Cells Chemical Agents Chemicals Class Cultured Cells Data Development Dinitrobenzenes Disruption Drug Formulations Drug Industry Economics Educational process of instructing Embryo End Point Endocrine Endocrine Disruptors Endocrine disruption Endocrine system Environmental Health Environmental Pollution Epithelial Epithelial Cell Proliferation Estrogen Receptors Estrogens Ethical Issues Evaluation Evolution Experimental Designs Experimental Models Exposure to Fetal Development Fluorescence Polarization Food Processing Gene Expression Goals Growth Health Hormonal Hormone Receptor Human Immune system In Vitro Industry Laboratories Lead Ligands MCF7 cell Malignant Epithelial Cell Malignant Neoplasms Mammary Neoplasms Methods Modeling Monitor Numbers Operative Surgical Procedures Paper Pesticides Phase Phytoestrogens Progesterone Receptors Public Health Reproducibility Reproduction Research Research Project Grants Risk Assessment Rodent Screening procedure Sensitivity and Specificity Signal Transduction Stratification Structure System Testing Thick Thyroid Gland Tissue Model Tissues Toxic effect Transformed Cell Line United States Environmental Protection Agency Uterus Vagina Validation Women&apos s Health base carcinogenesis cell growth cost enzyme activity estrogenic activity hazard hormone regulation human tissue in vitro Assay in vitro Model in vivo keratinization monolayer neoplastic cell receptor receptor binding receptor expression reproductive response species difference validation studies

项目摘要

DESCRIPTION (provided by applicant): Environmental or intentional exposure to a broad variety of chemical agents can alter normal endocrine function. The effects of these "endocrine disruptors" (ED) can have serious health implications including deleterious effects to reproductive capacity, fetal development, the immune system, and carcinogenesis. Current animal tests are expensive, use a large number of animals, and are not necessarily applicable to humans. Thus, a validated, human in vitro method to identify ED is an area of great importance. This research project will develop such a test method. Phase I research will prevalidate MatTek's organotypic vaginal- ectocervical (VEC-FT) tissue model for use in identifying endocrine disruptors (ED). A battery of 25 model compounds with known ED activity will be used. Changes to key hormonal receptors, enzyme activity, tissue structure, proliferation, and gene expression will be monitored. These data will be used to develop a prediction model that will be a sensitive and specific predictor of ED potential. During Phase II, the test method will undergo formal validation in a multi-center, GLP study. The prevalidated in vitro test to be developed for assessing the endocrine disrupting potential of chemicals/ formulations will have enormous environmental and public health significance. Evaluation of endocrine disruptors is important to minimize hazards to humans and wildlife exposed to chemicals that interfere with normal hormonal regulation. The proposed human organotypic tissue based assay will provide a sensitive and specific assay method to screen a large number of endocrine disrupting chemicals at a reduced cost.

描述（由申请人提供）：环境或故意接触多种化学剂可以改变正常的内分泌功能。这些“内分泌破坏者”（ED）的影响可能具有严重的健康影响，包括对生殖能力，胎儿发育，免疫系统和致癌作用的有害影响。当前的动物测试很昂贵，使用大量动物，不一定适用于人类。因此，鉴定ED的经过验证的人类体外方法是一个非常重要的领域。该研究项目将开发这种测试方法。第一阶段的研究将使Mattek的细胞型阴道诊断（VEC-FT）组织模型用于识别内分泌干扰物（ED）。将使用25种具有已知ED活动的模型的电池。将监测关键激素受体，酶活性，组织结构，增殖和基因表达的变化。这些数据将用于开发一个预测模型，该模型将是ED电位的敏感且特定的预测指标。在第二阶段，测试方法将在多中心的GLP研究中进行正式验证。为了评估化学/配方的内分泌干扰潜力的开发的体外测试将具有巨大的环境和公共卫生意义。内分泌干扰物的评估对于最大程度地减少对人类的危害和暴露于干扰正常荷尔蒙调节的化学物质的危害。拟议的人体器官组织测定法将提供一种敏感且特定的测定方法，以降低成本筛选大量内分泌破坏化学物质。