The tumor promoter phorbol-12,13-dibutyrate [P(Bu)2] stimulates cytotoxic activity of human blood lymphocytes.

The tumor promoters 12-13-phorbol-dibutyrate, P(Bu)2, and 12-O-tetradecanoylphorbol-13-acetate, TPA, were shown to augment the cytotoxic potential of human blood lymphocytes with low cell density. In kinetics experiments the enhancing effect was preceded by an initial suppression lasting for about 2 hours. Admixture of mononuclear adherent cells abrogated the P(Bu)2 effect in a dose dependent way. P(Bu)2 altered the sensitivity of K562 cells to the cytotoxic effect. Short term pretreatment increased the sensitivity, but after longer pretreatment the cells became resistant. The results show that tumor promoters can influence the cytolytic system at different levels. By acting directly on the lymphocytes they potentiate the lytic function. When mixed mononuclear populations are used, this effect may be counteracted via activation of the suppressive functions of monocytes. In addition, the target cell sensitivity can also be modulated. As a result, the final outcome of phorbol treatment depends on the strength, kinetics and the mode of its effects on the interactants.