The potent tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) acts synergistically with all known mitogens to induce DNA synthesis in 3T3 cells. In contrast, the neurohypophyseal hormone vasopressin, which is mitogenic for 3T3 cells, fails to synergize with TPA to stimulate DNA synthesis, ornithine decarboxylase activity or 2-deoxyglucose uptake. Thus TPA acts through a pathway which converges with that used by vasopressin, and at least some of its biological effects occur through mechanisms normally utilized by specific hormones.

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A transient exposure of cell cultures to 12-0-tetradecanoyl-phorbol-13-acetate (TPA) is sufficient to stimulate DNA synthesis during a subsequent incubation in TPA-free medium. We show that (1) a substantial fraction of TPA remains bound to cultures following a transient exposure to TPA and thorough washing, (2) the ability of TPA to induce DNA synthesis is a function of the amount of TPA bound to cell cultures irrespective of whether it is incubated continuously with cultures or transiently exposed to cultures under various conditions, and that (3) a transient exposure of cultures to phorbol-12-13-dibuytrate (PDB), a mitogenic phorbol ester which binds reversibly to cell cultures, does not stimulate DNA synthesis during a subsequent incubation in PDB-free medium. Therefore the persisting effects of TPA are due to it binding to cultures in a manner resistant to washing and not due to the induction of a stable cellular change prerequisite for mitogenesis. Further, we show that certain combinations of polypeptide growth factors induce DNA synthesis in the absence of any such stable cellular change. Evidence is also presented that the persisting effects on DNA synthesis following transient exposure of cultures to other polypeptide growth factors (e.g., platelet-derived growth factor) reflect tenacious binding rather than induction of a lasting biological event.