This application extends the phase I effort to develop """"""""polycos"""""""" vectors for high efficiency screening of mutagens in transgenic mice. Phase I results demonstrate the feasibility that this system may significantly improve upon existing shuttle vectors by increasing the assay speed and reducing the cost of existing transgenic assays. The system will permit quantitative, tissue specific determination of mutant frequencies. Coupled with additional quantitative measures (e.g., DNA adduct levels), it potentially 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 transgenic systems outlined under this proposal is anticipated to permit rapid DNA sequence characterization of mutations for assistance in determining the underlying mechanisms leading to those mutations.
