Induction of type-C retrovirus by the tumor promotor TPA.

The tumor promotor 12-0-tetradecanoyl-phorbol-13-acetate (TPA) induced endogenous murine xenotropic type-C retrovirus from A1-2 cells, derived from the BALB/c mouse, as determined by infectious center focus-forming assay on permissive normal rat kidney (NRK) cells. Kinetic dose-response studies showed that the number of cells induced to release virus was dependent on TPA concentration and the time of assay following TPA exposure. Maximal induction occurred when cells were treated with 80 ng/ml of TPA for 24 h and assayed at 24 or 48 h. A 30-min pulsed TPA exposure and 200 ng/ml induced virus levels approximating those observed after a continuous 24-h exposure to 80 ng/ml. The combination of TPA at concentrations of 10 and 20 ng/ml and a suboptimal level of 5-iodo-2-deoxyuridine (IdUrd) enhanced retrovirus induction threefold above that seen by the optimum IdUrd concentration alone. The protease inhibitors, antipain and leupeptin, decreased virus induction by TPA, a protease inducer. The capacity of TPA to induce type-C retrovirus complements results demonstrating the enhancement of Epstein-Barr virus (EBV) and murine mammary tumor virus (MMTV) synthesis by TPA.