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3阶段战略计划中引用的关键研究领域是将遗传多样性纳入体外筛查策略，以确定化学反应中的人群动态。这项研究利用从多样性的小鼠神经祖细胞中收集的裂解物，暴露于3种潜在的神经毒性剂，以12个化学浓度。在此分析过程中，我们将确定（1）将易感性与每种化学物质的非敏感小鼠线区分开的关键转录途径，（2）由转录状态定义的关键分子事件的出发点，以及（3）毒性动力学变异性因素，这些因素描述了多种化学响应在多样性中的不同化学响应的差异（do）。