Hepatitis B virus (HBV) and hepatitis C virus (HCV) are causally linked to hepatocellular carcinoma (HCC). Our goal is to understand how these two viruses induce HCC. HBV X gene has been implicated in cellular transformation. Thus, we will examine whether the X gene can cooperate with tumor promoters or liver injuries and regenerations to induce HCC. We will also characterize cellular factors that bind to the X protein. DS cell line is a cell line prepared from an HCV patient. Our preliminary experiments indicates that this cell line is persistently infected by HCV. We wish to further characterize this cell line, since, if it is indeed persistently infected by HCV, it will provide a good modal system for studying the replication of HCV RNA. In order to understand how HCV induces HCC, we will characterize the HCV gene products. We will also examine whether HCV gene products can cooperate with other oncogenes to transform primary rat hepatocytes.