The main objective of this project is to compare the initiated state in the neoplastic process that is brought about by either chemical carcinogens or retroviral associated oncogenes and to determine the phenotypic traits that characterize the initiation caused by these different carcinogenic agents. We are employing rat liver and established normal rat hepatocyte cell lines as models in these studies. The research is currently focused on: 1) transfecting rat liver cells with molecular chimeras of MMTV-v-ras, and other retroviral associated oncogenes that can be driven by glucocorticoid hormones and is known to transform 3T3 mouse fibroblasts; and 2) determine if morphologic transformation of the transfected hepatocytes is realized upon activation of the v-ras gene by dexamethasone. The results obtained so far include: 1) Rat hepatocyte cell lines derived from neonatal Fisher rats (FNRL-cells) were successfully transfected with pCneo10 plasmid, conferring G418 resistance. The transfection efficiency of the FNRL cells was about 25% of that observed in 3T3 cells. 2) Co-transfection of the FNRL cells with the neo-containing plasmid and the MMTV-v-ras chimera has resulted in isolation of several G418 resistant colonies that are presently being characterized.