Transgenic shuttle vector assays for assessing oxidative B-cell mutagenesis in vivo

The recent development of transgenic mutagenicity assays provides new oppor tunities for evaluating mutagenic processes in vivo. To assess mutant frequ encies in tissue B cells, we decided to take advantage of two such assays t hat utilize the transgenic shuttle vectors, lambda LIZ and pUR288. Our main interest in this research is to test two basic premises of inflammation-in duced plasmacytoma development in genetically susceptible BALB/c mice; i.e. , the possibility that plasmacytoma precursor cells may become targets of p hagocyte-mediated oxidative mutagenesis in situ and the prospect that plasm acytoma susceptibility/resistance genes may contribute to these phenotypes by enhancing/reducing oxidative mutagenesis in B cells. Based on our prelim inary experience with the lambda LIZ and pUR288 transgenic in vivo mutageni city tests, we propose to employ these assays as broadly applicable tools f or assessing overall mutagenesis during normal and aberrant (malignant) B-c ell development. Furthermore, transgenic shuttle vector assays appear to le nd themselves as ideal methods to associate general B-cell mutagenesis with the peculiar, B cell-typical somatic hypermutation processes that target t he V(D)J gene segment, the proto-oncogene bcl-6 and perhaps other, still un known loci.