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

Tox21第三阶段战略计划中提到的一个关键研究领域是将遗传多样性纳入体外筛选战略，以确定化学反应中的种群动态。本研究利用了从暴露于12种化学浓度的3种潜在神经毒性剂的多样性远交小鼠神经祖细胞中收集的裂解物。在该分析过程中，确定了（1）区分每种化学品敏感与不敏感小鼠品系的关键转录途径，（2）由转录状态定义的关键分子事件的出发点，以及（3）描述多样性远交（DO）小鼠种群内化学反应个体间差异的毒理学变异性因子。

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, (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, were determined.