In this proposal we describe an approach to define the molecular nature of x-ray induced mutants based on an integrated lambda phage shuttle vector which carries a target gene in which mutants can be scored and analyzed. This vector is amenable to study in vivo in transgenic mice as well as in cell culture systems. The availability of whole animals with recoverable shuttle vectors with target genes makes possible the study of physiologically relevant parameters in exposure to ionizing radiation. Some of these factors include dose-rate effects, tissue and organ specific differences, and age-related effects. 1. To construct transgenic mouse strains which contain integrated copies of a recoverable lambda phage based shuttle vector with target genes for mutagenesis. 2. To determine mutation frequencies in vivo in shuttle vector DNA residing in various tissues in the intact animal exposed to x- rays and selected chemical mutagens. 3. To determine the molecular nature of mutations in chromosomal DNA of cultured mammalian cells induced by x- rays.
