Abstract
The expansionable human hepatoma cell lines including HepG2 have potential for use in bio-artificial liver (BAL) systems for liver disease due to the shortage of donation. However, at present, BALs are incomplete and the functions need to be improved or at least maintained for a longer period. In this study, we aimed to establish novel hepatoma cell lines for a longer-term or permanent artificial livers. For this purpose, anti-apoptosis genes such as bcl-2, p35 and crmA were introduced into HepG2 cells. Over-expression of any of these genes significantly inhibited apoptosis. For example, after exposure to 51°C for 10 minutes, the viability of bcl-2, p35 and crmA transfectants were 8%, 27% and 16%, respectively, while that of wild type was 3%. Over-expression of anti-apoptosis gene prolonged the period of the stationary phase in the growth curve and did not affect the growth rate during the exponential phase. To test the liver function, cytochrome P-450 1A1 activity of transfectants were measureed. After induction with 3-methylcholanthrene, the cytochrome activity of bcl-2, p35 and crmA transfectants were 8.7, 9.4 and 7.7 fmol/cell/hour, respectively, while that of wild type was 7.0 fmol/cell/hour. Introduction of anti-apoptosis genes would be effective for the generation of novel hepatoma cell lines for artificial livers.
