Diversity supplement to link research and community engagement

摘要 污染已经成为一个日益严重的问题，对人类健康产生了负面影响。重金属 铅、六价铬和镉在美国各地都受到了污染。《国家报》 毒理学计划(NTP)专注于研究使用单一基因的毒理学影响 背景，B6C3F1。这就留下了遗传背景如何影响剂量反应的悬而未决的问题 这些毒物。与德克萨斯州环境健康科学农工中心成员合作 (蒂格尔)应激源的主题领域和个体对群体的反应，遗传背景 铅、六价铬或镉对单一金属口腔暴露后金属沉积的影响 作为可以连接这些主题领域的范例进行调查。为了模拟人类种群的多样性， 将使用来自协作杂交(CC)小鼠遗传参考种群的菌株。使用初步版本 来自用于铅沉积的大CC屏幕的数据，每金属处理四个CC菌株将用于标准 NTP类型14天暴露，以解决沉积、分子和细胞毒性机制的差异， 以及醋酸铅、重铬酸钠和氯化镉的微生物群失调。为了更好地模拟这些 暴露在美国，小鼠将保持在高脂肪，高碳水化合物的美国以前配方 为美国人的平均饮食消费建模。低剂量和高剂量的这些金属模拟人类 暴露将通过饮用水进行管理。除了通过演示使特切尔成员受益之外 如何将两个不同的主题领域整合在一起，这项研究将为 科学家正在接受培训，以增加环境卫生劳动力，并将更好地为发展提供信息 更可靠的毒性范围，并为差异反应的机理研究奠定基础 到重金属。此外，应聘者还将通过与 蒂格尔社区参与核心，帮助教育关注重金属影响的社区 以及蒂特尔是如何应对健康影响的。这也将使应聘者获得职业发展。 社区参与方面的经验。

SUMMARY Pollution has become an increasing problem with negative implications for human health. The heavy metals lead, hexavalent chromium, and cadmium have contaminated sites throughout the United States. The National Toxicology Program (NTP) has focused on investigating the toxicological effects using a single genetic background, B6C3F1. This leaves unanswered questions about how genetic background affects dose-response to these toxicants. In collaboration with members of the Texas A&M Center for Environmental Health Sciences (TICER) thematic areas of Stressors to Responses and Individuals to Populations, the genetic background affects metal deposition after single metal oral exposure to lead, hexavalent chromium, or cadmium will be investigated as an exemplar that can connect these thematic areas. To model diversity in the human population, strains from the Collaborative Cross (CC) mouse genetic reference population will be used. Using preliminary data from a large CC screen for lead deposition, four CC strains per metal treatment will be used in a standard NTP type 14-day exposure to address differences in the deposition, molecular and cellular mechanism of toxicity, and microbiome dysbiosis of lead acetate, sodium dichromate, and cadmium chloride. To better model those exposed in the US, mice will be maintained on a high-fat, high-carbohydrate American previously formulated to model the average dietary consumption of Americans. Low and high doses of these metals that model human exposures will be administered by drinking water. In addition to benefiting TICER members by demonstrating how two diverse thematic areas can be integrated, this study will provide an outstanding training platform for a scientist in training to increase the environmental health workforce and will better inform the development of more reliable toxicity ranges and establish the foundation for mechanistic studies underlying differential response to heavy metals. Additionally, the candidate will gain community engagement experience by working with the TICER Community Engagement Core to help educate communities of concern on the impact of heavy metal exposure and how TICER is addressing the health impacts. This will also allow the candidate to gain career experiences in community engagement.