The long-term objectives of the proposed Meharry Medical College ARCH Facility Core is to augment andexpand the capacity of the existing Inhalation Toxicology Facility and the Environment Toxicology laboratoryto perform B(a)P exposures, both inhalation and oral, and to assess tissue deposition of the toxin andmetabolites. Doing so will enable better quality control, while reducing costs to the individual investigatorand in case of the ARCH Program will facilitate the understanding of the molecular mechanism of B(a)Ptoxicity. 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 systemunder study in each ARCH research/pilot project, and 2) To continually enhance and refine technology. Asan example, we are exploring introducing state-of-the-art single-cell nanobiosensor technology for theanalysis 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 haveextensive 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 thedevelopment of a more mechanistic approach in all projects. For example, Dr. Ramesh and Dr. Morrow aretesting the hypothesis that B (a) P exposure will accelerate the progression of colon cancer using the PacMin+/- transgenic mouse model. Similarly, the hypothesis of Drs. Ogunkua and Matusik is that B(a)Pexposure will shift the dose-response curve to the left with respect to the progression from pre-neoplastic focito the adenocarcinoma in the 12t-7f transgenic LADY mouse model. Drs. Ansah and Deutch will employ theuse of C57BL/6J mice, as this will offer them the opportunity to test their hypothesis in transgenic mice thatoverexpress antioxidant enzymes. In the case of the Hood/Aschner project, the shift from rats to mice willallow 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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