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策略，以确定化学反应中的种群动态。这项研究利用从多样性繁殖的小鼠神经前体细胞收集的裂解物，暴露于12种化学浓度下的3种潜在神经毒剂。在这一分析过程中，我们将确定(1)区分每种化学物质敏感和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起点，以及(3)描述多样性近交系(DO)小鼠群体内化学反应个体间差异的毒理变异性因素。

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.