Antiviral agents in hepatitis B virus transfected cell lines: inhibitory and cytotoxic effect related to time of treatment.

The antiviral and cytotoxic effects of ara-arabinoside monophosphate, 2',3', dideoxy-cytidine, ganciclovir, 9-2(-phosphonylmethoxyethyl) adenine, 2',3'-dideoxy-3'-thiacytidine and recombinant interferon-alpha were studied using two human hepatitis B virus transfected hepatoma cell lines, HepG2 2.2.15 and HB 611. After 9 days of exposure, starting on day 3 after seeding, inhibition of extracellular HBV-DNA expressed as ID50 was in the 0.1-1.0 microM range for 2',3'-dideoxy-3'-thiacytidine and 9-2(-phosphonylmethoxyethyl) adenine and > 10 microM for dideoxy-cytidine, ara-arabinoside monophosphate and ganciclovir in both cell lines. At 2.500 U/ml recombinant interferon-alpha showed less than 20% inhibition in both cell lines. The HBV-DNA inhibitory effects of 2',3'-dideoxy-3'-thiacytidine and 9-2(-phosphonylmethoxyethyl) adenine were also investigated after 1 and 3 days of exposure. In that setting ID50's were 10 and 3.3 microM for 2',3'-dideoxy-3'-thiacytidine and > 100 and 30 microM for 9-2(-phosphonylmethoxyethyl) adenine, respectively. No major inhibitory effect on hepatitis B surface antigen and hepatitis B e antigen secretion was observed for any agent in this study, except for 9-2(-phosphonylmethoxyethyl) adenine in HB 611 cells. Cytotoxicity measured by inhibition of [3H-methyl] deoxythymidine incorporation and expressed as CD50 on day 4 was in the 10-100 microM range for ara-arabinoside monophosphate; in the 100-1000 microM range for 9-2(-phosphonylmethoxyethyl) adenine, ganciclovir and dideoxy-cytidine; and > 1000 microM for 2',3'-dideoxy-3'-thiacytidine.(ABSTRACT TRUNCATED AT 250 WORDS)