Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line

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Abstract
A significant aspect of primary hepatic carcinoma in man is the high positive correlation of hepatocelhilar carcinoma with infection with hepatitis B virus (HBV)1. Analysis of the relationship between HBV infection and oncogenesis is difficult because natural infection with HBV is limited to man and experimental infection has been achieved only in chimpanzees and gibbons. Furthermore, because HBV has not been successfully propagated in cell culture, basic study of virus–cell interaction of the aetiological agent of one of the most widespread infections of man has been impossible2. Recently, however, a cell line (PLC/PRF/5) derived from a human hepatoma biopsy was described3 which produces the HBV surface antigen (HBsAg) and so provides a tool for the experimental investigation of HBV in vitro. We now report the derivation and characterisation of two additional cell lines from primary liver carcinomas. In contrast to the PLC/PRF/5 cell line, these cell lines retain the capacity to synthesise many human plasma proteins, including both albumin and α-fetoprotein (AFP). One of these lines also produces HBsAg. We also present evidence that HBsAg synthesis and secretion in this cell line are correlated with the growth state of the culture. This finding is in contrast to the continuous HBsAg production found in the PLC/PRF/5 cell line.