CORE--ARCH Facility

核心--拱门设施

• 批准号: 7161191
• 负责人: Darryl Brice Hood
• 金额: $ 14.55万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7161191
• 关键词: adenocarcinoma; air pollution; benzopyrenes; biomedical facility; chemical carcinogenesis; colon neoplasms; disease /disorder model; environmental exposure; environmental toxicology; food contamination; genetic models; genetically modified animals; laboratory mouse; technology /technique development

The long-term objectives of the proposed Meharry Medical College ARCH Facility Core is to augment and expand the capacity of the existing Inhalation Toxicology Facility and the Environment Toxicology laboratory to perform B(a)P exposures, both inhalation and oral, and to assess tissue deposition of the toxin and metabolites. Doing so will enable better quality control, while reducing costs to the individual investigator and in case of the ARCH Program will facilitate the understanding of the molecular mechanism of B(a)P toxicity. The Short term aims are: 1) To provide a well-integrated facility core to provide for the purchase, exposure, animal husbandry and analysis of B (a) P parent compound/ metabolites from each organ system under study in each ARCH research/pilot project, and 2) To continually enhance and refine technology. As an example, we are exploring introducing state-of-the-art single-cell nanobiosensor technology for the analysis of B(a)P metabolites in single cells or small cell groups, for future studies by our investigators. The Inhalation Toxicology Facility is Directed by the PD, Dr. Darryl Hood, while an ARCH investigator, Dr. Aramandla Ramesh, directs the Environmental Toxicology laboratory. Both of the investigators have extensive experience relative to their responsibility to this core. Mice models will be used to exploit the use of transgenic mice when appropriate so as to allow for the development of a more mechanistic approach in all projects. For example, Dr. Ramesh and Dr. Morrow are testing the hypothesis that B (a) P exposure will accelerate the progression of colon cancer using the Pac Min+/- transgenic mouse model. Similarly, the hypothesis of Drs. Ogunkua and Matusik is that B(a)P exposure will shift the dose-response curve to the left with respect to the progression from pre-neoplastic foci to the adenocarcinoma in the 12t-7f transgenic LADY mouse model. Drs. Ansah and Deutch will employ the use of C57BL/6J mice, as this will offer them the opportunity to test their hypothesis in transgenic mice that overexpress antioxidant enzymes. In the case of the Hood/Aschner project, the shift from rats to mice will allow for the of transgenic mouse models which has a "built in" advantage for future studies that will use +/- and -/- knockouts on this C57BL background.

拟议的Meharry医学院拱门设施核心的长期目标是增加和 扩大现有吸入毒理学设施和环境毒理学实验室的能力 要执行B（a）P暴露，包括吸入和口服，并评估毒素的组织沉积和 代谢物。这样做将实现更好的质量控制，同时降低个人调查员的成本 如果拱门程序将有助于理解B（a）p的分子机制 毒性。短期目的是：1）提供一个整合的设施核心，以提供购买， 来自每个器官系统的B（a）p父级化合物/代谢物的暴露，畜牧业和分析 在每个ARCH研究/试点项目中进行的研究，以及2）不断增强和完善技术。作为 一个例子，我们正在探索引入最先进的单细胞纳米传感器技术 分析单细胞或小细胞组中的B（a）P代谢物，用于我们的研究者将来的研究。 吸入毒理学设施由PD Darryl Hood博士指导，而Arch调查员博士 Aramandla Ramesh指导环境毒理学实验室。两个调查人员都有 相对于他们对这个核心的责任，丰富的经验。 小鼠模型将在适当时使用转基因小鼠的使用来利用使用 在所有项目中开发更机械的方法。例如，拉梅什博士和莫罗博士是 测试B（a）p暴露将使用PAC加速结肠癌的进展的假设 最小+/-转基因小鼠模型。同样，DR的假设。 ogunkua和matusik是B（a）p 暴露会将剂量反应曲线转移到左侧的左侧，相对于肿瘤前灶的进展 在12T-7F转基因LADY小鼠模型中进入腺癌。博士。安萨和迪特将采用 使用C57BL/6J小鼠，因为这将使他们有机会在转基因小鼠中测试其假设 过表达抗氧化剂酶。对于Hood/Aschner项目，从老鼠到老鼠的转变将 允许将未来研究具有“内置”优势的转基因小鼠模型，该模型将使用+/- 和 - / - 敲除此C57BL背景。