The tumor-promoting phorbol esters have proven to be potent immunomodulatory agents in vitro. It has not been possible to assess the role of phorbol ester-induced alterations of immune function in tumor promotion however, due to a lack of in vivo studies. Studies were therefore designed to assess proliferative responses of murine leukocytes after in vivo exposure to these agents. Topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) was found to cause an increase in division of murine spleen cells. The effect was dose-related up to 14 micrograms per application and generally reached a peak two days after TPA application. Cell separation experiments suggested TPA was acting on an adherent cell population distinct from splenic lymphocytes. Inflammatory reactions to TPA followed a similar time-course to that observed for spleen cell proliferation. The increased levels of proliferation observed could, therefore, be due to increased division of neutrophil and/or macrophage precursors residing in the murine spleen and appeared also to be associated with the inflammatory reaction induced by TPA.
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