Inhibitory Effect of Interferon on Cellular DNA Synthesis: Modulation by Pure mitogenic Factors

Abstract

Quiescent Swiss 3T3 mouse cells can be stimulated to synthesize DNA by combinations of polypeptide hormones [insulin, vasopressin, epidermal growth factor, fibroblast-derived growth factor], retinoids [retinoic acid] and tubulin-disrupting agents [colchicine]. Low doses of mouse interferon are effective in inhibiting DNA synthesis induced by 1, 2 or 3 factors. When more growth factors are added, DNA synthesis is not further stimulated, although the dose response curve for interferon is shifted dramatically to the right. Even when added before the mitogenic stimulus, up to 2000 U of interferon have no effect on DNA synthesis stimulated by 5 factors. A change in the dose-response curve for interferon as an antiviral agent [vs. encephalomyocarditis virus] is also observed when the mitogenic stimulation is increased, but the effect is less dramatic than that observed on its function as an inhibitor of DNA synthesis.