ARCH Facility Core

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 Environmental 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 the 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 for the purchase, exposure, and husbandry of animals, in addition to the analysis of B(a)P parent compound/metabolites from the organ systems under study in each ARCH research or pilot project, and 2) to continually enhance and refine technology. For instance, investigators 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 to be used in future studies. The Inhalation Toxicology Facility is directed by the Program Director, Dr. Darryl Hood, and ARCH investigator, Dr. Aramandla Ramesh, directs the Environmental Toxicology laboratory. Both investigators have extensive experience relevant to their responsibility in this core. Mice models will be used to exploit the use of transgenic mice when appropriate to allow for the development of a more mechanistic approach in all projects. For example, Drs. Ramesh and 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 research project of Drs. Hood and Aschner, the shift from rats to mice will allow use of a transgenic mouse model which has a "built in" advantage for future studies that will use +/- and -/- knockouts on this C57BL background.