The Hepatobililiary Disease Group conducts hepatic toxicologoy research, develops in vitro alternatives for conventional hepatic toxicity and carcinogenesis studies, and engages in independent research on bile acids. In vitro studies are conducted using short and long term cultures of primary hepatocytes. Research goals are (1)to characterize mechanisms involved in hepatocellar toxicity and carcinogenicity of bile acids specifically related to alterations in intracellular transport and metabolism and (2)to determine if endogenous concentrations of an important primary bile acid that are increased by treatment with a compound that is a hepatocarcinogen are involved in the carcinogenic process. These studies will (1)identify specific drugs, compounds and/or disorders that, through alterations in hepatocellular processing of bile acids, produce or modify hepatic toxicity and carcinogenicity and (2)demonstrate that increases in endogenous concentrations of a primary bile acid can promote the formation of neoplastic lesions in liver. This finding would indicate that specific changes in endogenous bile acid concentrations can contribute to hepatocarcinogenicity associated with other treatments and diseases.