Modulation of the interferon antiviral activity by adriamycin in human cells in culture

The antiviral activity of exogenously applied HuIFN-alpha was significantly reduced in cells pretreated with non-toxic concentrations of adriamycin. With low concentrations of adriamycin (up to 0.125 micrograms/ml) the effect was reversible in all cells tested. In human foreskin (BG-9) cells, that are more resistant to adriamycin toxicity, higher nontoxic concentrations of adriamycin (0.625 micrograms/ml) caused an irreversible decrease in sensitivity to HuIFN-alpha. Under these conditions, adriamycin pretreatment irreversibly inhibited the rate of cellular protein synthesis in BG-9 cells by about 30%. In contrast, cellular RNA synthesis was inhibited by 80% in 4 h after exposure to the drug, but was restored to almost normal levels (97% of control) at day 4 after removal of the drug. These results suggest that the loss of sensitivity of adriamycin-treated BG-9 cells to HuIFN-alpha may be related to the inhibition of cellular protein synthesis.