Effect of Human Fibroblast Interferon on the Antiviral Activity of Mammalian Cells Treated with Bleomycin, Vincristine, or Mitomycin C¹

Bleomycin, vincristine, or mitomycin C, when added to HeLa cells simultaneously with human fibroblast interferon (IFN-β), caused a decrease in cell density and inhibited DNA synthesis compared with HeLa cells treated with IFN-β alone. However, the IFN-β-induced antiviral processes were unaffected by the presence of these drugs as determined by in vitro enzyme assays and the development of the antiviral state in the intact HeLa cell. HeLa cells treated with IFN-β alone or with IFN-β in combination with bleomycin, vincristine, or mitomycin C were able to induce the double-stranded RNA-dependent adenosine triphosphate:2′,5′-oligoadenylic acid adenyltransferase (EC 2.2.2.-) and the double-stranded RNA-dependent protein kinase. Furthermore, the antiviral state as measured by the reduction of plaqueforming units after infection of treated cells (with IFN-β alone or with IFN-β plus drugs) with vesicular stomatitis virus was not affected. These results indicate that, under these experimental conditions, the double-stranded RNA-dependent adenosine triphosphate:2′,5′-oligoadenylic acid adenyltransferase and protein kinase can be induced by IFN-β in cells treated with bleomycin, vincristine, or mitomycin C. These cells also develop the antiviral state. These experiments could provide a basis for a careful examination of the effects of interferon on the development of the antiviral state when testing potentially active antineoplastic agents. The possibility that IFN-β potentiates the cytotoxic effects of bleomycin and mitomycin C on HeLa cells is also discussed.