Comparative effects of a complete tumor promoter, TPA, and a second-stage tumor promoter, RPA, on intercellular communication, cell differentiation and cell transformation.

The biological activities in vitro of the incomplete (second-stage) tumor promoter, 12-O-retinoyl phorbol-13-acetate (RPA), and the complete tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) were compared. The doses of TPA and RPA necessary to inhibit the specific binding of [3H]-phorbol-12,13-dibutyrate ([3H]PDBu) to BALB/c 3T3 cells (50% inhibition doses; ID50; 8-13 ng/ml) were very similar; however, RPA was less potent than TPA in inhibiting [3H]-PDBu binding to Friend erythroleukemia cells (FELC). Intercellular communication between BALB/c 3T3 cells, measured by transfer of microinjected fluorescent dye (Lucifer Yellow), was inhibited by RPA as well as by TPA; TPA was about five times more potent than RPA. RPA also inhibited FELC differentiation induced by hexamethylene bisacetamide (HMBA) but not the differentiation of a TPA-resistant clone. The dose-responses of these two compounds in inhibiting differentiation of both TPA-sensitive and resistant FELC were very similar. When TPA and RPA were compared in their promoting activity of in vitro cell transformation of BALB/c 3T3 cells initiated with 3-methylcholanthrene (MCA, 0.1 microgram/ml), both TPA and RPA significantly increased the yield of morphologically transformed foci, and RPA was approximately 10 times more potent than TPA. These results suggest that RPA and TPA share many common in vitro biological effects and that these in vitro studies do not allow us to delineate clearly the effect of a second-stage tumor promoter from that of complete tumor promoters such as TPA.