CORE--ARCH Facility

拟议的梅哈里医学院核心设施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 进行吸入和口服B（a）P暴露，并评估毒素的组织沉积， 代谢物。这样做将能够更好地进行质量控制，同时降低个体研究者的成本 如果是化学计量学程序，将有助于理解B（a）P的分子机制 毒性短期目标是：1）提供一个良好的综合设施核心，以提供购买， 暴露、动物饲养和每个器官系统中B（a）P母体化合物/代谢物的分析 在每个可持续发展研究/试点项目中进行研究，以及2）不断提高和改进技术。作为 例如，我们正在探索引入最先进的单细胞纳米生物传感器技术， 分析单细胞或小细胞群中的B（a）P代谢物，以供我们的研究人员将来研究。 吸入毒理学机构由PD，Darryl Hood博士指导，而一名研究员， Aramandla Ramesh，环境毒理学实验室主任。两位调查员都 与他们对这一核心的责任相关的丰富经验。 小鼠模型将用于在适当时开发转基因小鼠的使用，以允许在小鼠中进行基因表达。 在所有项目中制定更加机械的方法。例如，Ramesh博士和Morrow博士 使用Pac检验B（a）P暴露将加速结肠癌进展的假设 Min+/-转基因小鼠模型。类似地，Ogunkua和Matusik博士的假设是，B（a）P 暴露将使剂量-反应曲线相对于肿瘤前病灶的进展向左移动 12 t-7 f转基因LADY小鼠模型中的腺癌。Ansah和Deutch博士将雇用 使用C57 BL/6 J小鼠，因为这将为他们提供机会，在转基因小鼠中测试他们的假设， 过表达抗氧化酶。在Hood/Aschner项目中，从大鼠到小鼠的转变将 考虑到转基因小鼠模型的“内置”优势，未来的研究将使用+/- 和-/-敲除在这个C57 BL背景上。

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.