Response of Drosophila embryonic cells to tumor promoters.

Several recent observations on tumor promoters point to the many developmental and embryonic characteristics associated with their mode of action. These observations have led us to investigate the effects of a series of tumor promoters on Drosophila embryonic cultures at both the morphological and molecular levels. The cultures have been used with some success by us to assess the teratogenic potential of a large number of molecules, including drugs, chemicals, and environmental pollutants. In this culture system, 12-O-tetradecanoylphorbol 13-acetate (TPA), the most potent of the tumor promoters tested, disrupted normal muscle and neuron differentiation at concentrations ranging from 0.1 to 10 microM; 4-O-methylphorbol 12-myristate a weak stage I promoter, used at concentrations the same as or higher than those of TPA had no inhibitory effect on cell differentiation. A selected group of tumor promoters was also investigated at the molecular level for their effects on differentiating Drosophila cells. All tumor promoters tested induced synthesis of three heat shock proteins. On the basis of these two levels of effects (morphological and molecular) it is apparent that the tumor promoters tested act similarly as teratogens do in the Drosophila embryonic cultures. This finding confirms some recent published reports suggesting that a large number of tumor promoters act as teratogens if the exposure interval is during the embryonic rather than the adult stage. We suggest that this system can be usefully employed to investigate some of the common mechanisms involved in tumor promotion and teratogenesis.