OF WORK: We use the transgenic Big Blue system to study gene mutations in vivo. Both the lacI and the lambda-cII genes are present in Big Blue mice and rats allowing for comparative in vivo mutagenesis studies. We have characterized lacI mutations in the liver of Big Blue mice following treatment with B[a]P followed by a partial hepatectomy. Both GC>TA and GC>CG transversions were found to be significantly elevated at hepatectomy and at sacrifice as compared to untreated control animals. These data suggest that BPDE adducts at guanine and adenine are primarily responsible for gene mutations in vivo following B[a]P treatment. In addition, we have derived primary Big Blue fibroblast mouse and rat cell strains that allow for direct in vitro comparisons of mutational and cytogenetic responses. In addition, we are evaluating other transgenic in vivo mutational assay systems for their utility in assessing specific types of DNA damage. The gpt-delta mouse appears to be useful for detecting gene mutations at the gpt locus and using the Spi- selection system one can detect gene deletions as well. This system may be a useful complement to the Big Blue? transgenic mouse, especially when assessing the genetic response to damage that is likely to cause large deletions and genomic rearrangements.
