This proposal outlines the development of transgenic mice containing a novel """"""""polycos"""""""" shuttle vector for in vivo testing of mutagens. This system has the potential of significantly improving existing shuttle vector systems by increasing the assay speed, and efficiency, as well as the cost of transgenic assays. This system will permit quantitative tissue specific determination of mutant frequency, and coupled with additional quantitative measures, such as DNA adduct levels, will allow for direct determination of the contribution of metabolic processes, cell proliferation, detoxification, DNA repair, and the route of chemical administration on mutagenesis. In addition, the proposed transgenic system will permit rapid DNA sequence characterization of mutation to aid in determining the underlying mechanisms leading to mutations.
