Suppression of lectin-stimulated DNA synthesis in bovine lymphocytes by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate.

12-O-Tetradecanoylphorbol-13-acetate (TPA) modulates DNA synthesis in bovine lymph node lymphocytes in culture. Whether TPA enhances or depresses DNA synthesis depends on when the TPA is added with regard to time of mitogenic stimulation. We have previously reported that TPA acts as a comitogen when added with the lectins phytohemagglutinin or concanavalin A, but it inhibits DNA synthesis in these cells in mixed lymphocyte culture. We report in this study that pretreatment of bovine lymph node lymphocytes with TPA depressed their proliferative response to phytohemagglutinin, concanavalin A, or pokeweek mitogen. The extent of inhibition varied somewhat with each animal and particular lectin. The effect was reversible. Inhibition was not due to a shift in the kinetics of the response or to a change in the dose response. TPA may act directly by changing the lymphocyte surface properties and/or indirectly through a cell population or product to suppress the proliferative response. One cell product, plasminogen activator, was identified in culture medium, although we have no evidence at this time that it is responsible for the inhibitory effect of TPA.