Effects of the Tumor Promoter 12-O-Tetradecanoylphorbol-13-acetate on Neurite Outgrowth from Chick Embryo Sensory Ganglia1

The addition of the phorbol ester 12-O-tetradecanoylphorbol13-acetate (TPA) to defined growth medium stimulated an in tense neurite outgrowth from chick sensory ganglia expiants. The development of radial neuntes was concentration depend ent. At low concentrations of TPA (1.6 to 16 nw), neuntes were long but moderate in numbers. At higher concentrations (160 to 480 nM), TPA produced dense, short neurites that formed thick fascicles. This reduced outgrowth in length was not related to cytotoxicity and was found to be reversible when the tumorpromoting agent was removed. Neurite outgrowth was also accompanied by an increase in proliferation of nonneuronal cells. Blocking the proliferation of nonneuronal components by the mitotic inhibitor 1-/3-o-arabinof uranosylcytosine did not inhibit neurite outgrowth, suggesting that the TPA-induced neurite dif ferentiation was independent of nonneuronal cells. When TPA was tested in the presence of nerve growth factor, the induction of neurite differentiation was not affected. Other active tumor promoters including phorbol-12,13-didecanoate and mezerein also elicited neurite outgrowth, while nonpromoting agents such as phorbol and 4«-phorbol-12,13-didecanoate were ineffective.