287 POTENTIAL ROLE OF INTERCELLULAR COMMUNICATION IN MORPHOGENESIS OF HYDRA REAGGREGATES

Abstract

An association between teratogenesis and carcinogenesis is suggested by clinical and experimental observations. Accumulating evidence supports a role for direct, junction-mediated intercellular communication in the coordination of cell proliferation and differentiation. Interruption of this intercellular communication may be a common mechanism of teratogenesis and carcinogenesis. We are testing this hypothesis using hydra reag-gregation as a developmental model. Hydra reaggregates were exposed to structurally related phorbol compounds. Some of these compounds are tumor promoters, inhibit junctional communication and are embryotoxic to amphibian and mammalian systems. We found that the ability of these compounds to interrupt hydra reaggregation correlated with their ability to promote tumor formation in mouse skin and inhibit junctional communication in an in vitro cell system. The strong tumor promoters, 12-0-tetradecanoyl-phorbol-13-acetate (TPA) and phorbol-12, 13-didecanoate, were much more potent (>100-fold) in their ability to disrupt hydra reaggregation compared to the weakly promoting compounds, phorbol-12, 13-diacetate and 4-0-methyl-TPA. This correlation supports the hypothesis that the phorbol compounds may induce tumor formation and abnormal development by similar mechanisms. We are currently exploring whether the phorbol compounds inhibit junctional communication in the actual reaggregating hydra, and whether the morphological characteristics of the junctions are altered.