CORE--ARCH Facility

拟议的梅赫里医学院ARCH设施核心的长期目标是加强和 扩大现有吸入毒理设施和环境毒理实验室的能力 进行吸入和口服的B(A)P暴露，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，同时降低个别调查员的成本 ARCH程序将有助于理解B(A)P的分子机制 毒性。短期目标是：1)提供一个整合良好的设施核心，为采购做好准备， 各器官系统中苯并(A)磷母化合物/代谢物的暴露、饲养和分析 在每个ARCH研究/试点项目中进行研究，以及2)不断提高和改进技术。AS 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苯并(A)磷代谢物，以供我们的研究人员未来研究。 吸入性毒理学设施由警察局达里尔·胡德博士领导，而ARCH研究员达里尔·胡德博士。 阿拉曼德拉·拉梅什是环境毒理学实验室的负责人。两名调查人员都有 具有丰富的经验，与他们对这个核心的责任有关。 在适当的时候，将使用小鼠模型来开发转基因小鼠的使用，以便允许 在所有项目中开发更机械化的方法。例如，拉梅什博士和莫罗博士 使用Pac检验苯并(A)P暴露将加速结肠癌进展的假设 Min+/-转基因小鼠模型。同样，奥贡库瓦博士和马图西克博士的假设是B(A)P 照射会使剂量-反应曲线相对于癌前病变的进展向左移动 12T-7f转基因Lady小鼠模型中的腺癌。Ansah博士和Deutch博士将利用 使用C57BL/6J小鼠，因为这将为他们提供在转基因小鼠中检验他们的假设的机会 过度表达抗氧化物酶。就Hood/Aschner项目而言，从大鼠到小鼠的转变将 考虑到转基因小鼠模型的出现，这对未来使用+/-的研究具有“内置”优势 和-/-在这个C57BL背景上的击倒。

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.