The goal of the proposed research is to establish whether hormone treatment and/or virus infection can cause biochemically active, well differentiated, non-proliferating adult isolated rat hepatocytes to proliferate and express fetal gene products. In the coming year, we will attempt to transform hepatocytes with HCMV and HSV-2 using sheared HSV-2 DNA and hepatocytes isolated from regenerating liver. SV40 transformed hepatocytes will be cloned and characterized for expression of SV40 antigens, release of infectious SV40, ultrastructure, expression of liver specific proteins, the presence of dexamethasone receptors, etc. Transformation with SV40 will be repeated in hepatocytes isolated from inbred rats and using a temperature sensitive SV40 mutant. The subsequent transformants will be characterized and tested for their ability to form tumors in animals. Experiments will also be carried out to determine whether HSV-2 infection stimulates division of hepatocytes, and whether this stimulation can be potentiated by hormones and growth factors. We will also determine the effects of HSV-2 and HCMV infection on the expression of liver specific proteins.