SUPPORT FOR THE CONDUCT OF STUDIES TO EVALUATE TOXICOGENOMIC RESPONSE OF DO MOUSE CELL LINES EXPOSED TO CHEMICALS FOR THE NTP

支持开展研究以评估暴露于 NTP 化学品的 DO 小鼠细胞系的毒理学反应

• 批准号: 10026342
• 负责人: BARNEY SPARROW
• 金额: $ 0.17万
• 依托单位: BATTELLE MEMORIAL INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-26 至 2019-09-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10026342
• 关键词: Area; Chemicals; Event; Exposure to; Genetic Transcription; Genetic Variation; Genomics; In Vitro; Mercury; Molecular; Mouse Cell Line; Mus; Pathway interactions; Phase; Population; Population Dynamics; Research; Strategic Planning; Toxicogenomics; nerve stem cell; neurotoxic; response; screening

A critical research area cited in the Tox21 Phase 3 strategic plan is incorporation of genetic diversity in in vitro screening strategies to determine population dynamics in chemical response. This study leverages lysates collected from Diversity Outbred mouse neural progenitor cells exposed to 3 potentially neurotoxic agents at 12 chemical concentrations. In the course of this analysis, we will determine (1) key transcriptional pathways that distinguish susceptible from nonsusceptible mouse lines for each chemical, (2) points of departure for key molecular events as defined by transcriptional status, and (3) toxicodynamic variability factors that describe interindividual differences in chemical response within the Diversity Outbred (DO) mouse population.

Tox21 第三阶段战略计划中引用的一个关键研究领域是将遗传多样性纳入体外筛选策略，以确定化学反应中的群体动态。这项研究利用了从 Diversity Outbred 小鼠神经祖细胞中收集的裂解物，这些细胞暴露于 12 种化学浓度的 3 种潜在神经毒性剂。在分析过程中，我们将确定（1）区分每种化学物质的易感小鼠系和非易感小鼠系的关键转录途径，（2）由转录状态定义的关键分子事件的出发点，以及（3）毒效动力学变异因素描述了多样性远交 (DO) 小鼠群体中化学反应的个体间差异。