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.
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