Analysis of developmentally homogeneous neural crest cell populations in vitro: II. A tumor-promoter (TPA) delays differentiation and promotes cell proliferation

The tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) delayed pigmentation in developmentally homogeneous quail neural crest cell populations in vitro. Doses below 5 × 10^?8M resulted only in a delay in pigmentation for up to 2 days without changing the rate of pigmentation, whereas intermediate doses (5 × 10^?8–10^?7M) delayed the initiation and decreased the rate of pigmentation but had no effect on the ultimate fate. Doses of TPA above 2 × 10^?7M irreversibly prevented pigmentation in some of the cells. TPA did not influence growth of the undifferentiated cell population. Since TPA delayed the decline in the cell proliferation rate that normally occurred with pigmentation, however, the final number of pigmented cells could be increased up to 10-fold in TPA-treated cultures without changing the homogeneity of the cultures. A part from the effects on cell differentiation, TPA caused an immediate change in cellular association within the clusters.