Development of in vitro toxicity expression assays

体外毒性表达测定的发展

• 批准号: 6841043
• 负责人: Gwo-Jen Day
• 金额: $ 9.77万
• 依托单位: ICONIX PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6841043
• 关键词: DNA damage; animal tissue; antineoplastics; bioassay; biomarker; biotechnology; cholestasis; cytotoxicity; dosage; drug adverse effect; gene expression; gene expression profiling; hepatotoxin; high throughput technology; liver cells; microarray technology; polymerase chain reaction; technology /technique development; toxicant screening; toxicology; toxin

DESCRIPTION (provided by applicant): The goal of this proposal is to develop and validate a process for generating in vitro, gene expression assays for toxicology. Specifically, we propose to derive gene signatures, that can classify chemicals according to specific liver pathology endpoints, using whole genome expression profiling in rat primary hepatocytes in vitro and to convert the gene signatures into efficient, high throughput, validated assays for use as a cost efficient, fast screening tool. The project will utilize the joint expertise of Iconix researchers in identifying toxicological gene signatures using compound treatment and global, microarray gene expression analysis, and Althea researchers for translating these signatures into high throughput gene expression assays using highly multiplexed, universal-primed rtPCR (UP-rtPCR). In this Phase I proposal, we intend to demonstrate the process for one general hepatoxicity endpoint, Cholestatis, and one general toxicity endpoint, DNA damage.

描述（由申请人提供）： 本提案的目标是开发和验证用于生成毒理学体外基因表达测定的过程。具体而言，我们建议获得基因签名，可以根据特定的肝脏病理学终点，在体外大鼠原代肝细胞中使用全基因组表达谱对化学品进行分类，并将基因签名转换为高效，高通量，经验证的检测方法，用作具有成本效益的快速筛选工具。该项目将利用Iconix研究人员的联合专业知识，使用化合物处理和全球微阵列基因表达分析来识别毒理学基因签名，以及Althea研究人员将这些签名转化为高通量基因表达检测，使用高度多重的通用引物rtPCR（UP-rtPCR）。在本I期提案中，我们打算证明一种一般肝毒性终点（胆汁淤积）和一种一般毒性终点（DNA损伤）的工艺。