Initial studies have shown that DNAs from thymic lymphomas induced in (AKR X RF)F1 mice by chemical carcinogen or radiation treatment contain activated N-ras or activated K-ras oncogenes, respectively. Several strains of mice treated similarly will be surveyed for oncogene activation using the technique of DNA-mediated gene transfer in two assays: (1) an in vitro assay to screen for ras oncogenes and (2) an in vivo assay utilizing nude mice to screen for new oncogenes. The anomalous expression of TL antigen on these tumors precedes the development of overt disease and will be used to follow and fractionate subpopulations of thymocytes from treated mice during the latent period. Immunohistochemistry of normal and leukemic tissue will be used to detect the expression of the ras gene product (p21 protein) and to determine the temporal relationship between ras and TL gene expression during the latent period of tumor development. Thymomas will be analyzed for chromosomal abnormalities, particularly trisomy 15, to identify correlations between specific chromosome changes and changes in gene expression. These studies should further our understanding about the genes involved in the malignant process and at what stages they may act.
