EFFECT OF '-(2,2,2-TRICHLOROETHYLIDENE)-BIS(4-CHLOROBENZENE) (DDT) ONGAP JUNCTIONAL INTERCELLULAR COMMUNICATION AND MORPHOLOGICAL TRANSFORMATION OF SYRIAN-HAMSTER EMBRYO CELLS

The organochlorine insecticide 1'-(2,2,2-trichloroethylidene)bis(4-chl orobenzene) (DDT) did not induce or promote induction of morphological transformation in Syrian hamster embryo (SHE) cells, but it was a pot ent inhibitor of gap junctional intercellular communication (GJIC). Th e kinase inhibitor staurosporine did not affect DDT induced inhibition of GJIC, although it has been shown to decrease the inhibitory effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on GJIC. In addition, p retreatment with TPA made the cells refractory to further TPA induced inhibition of GJIC, while they remained sensitive to DDT. Thus, DDT an d TPA inhibit GJIC through different mechanisms. Elevation of cellular cyclic adenosine monophosphate (cAMP) level by exposure to forskolin counteracted the inhibitory effect of DDT similar to that observed for TPA. Continuous exposure to DDT at concentrations near the effective concentration (50%) value (EC(50) value) resulted in a slight recovery of GJIC following the initial inhibition. This recovery was not accom panied by the cells becoming refractory to further DDT induced inhibit ion of GJIC. The recovery of GJIC after removal of the DDT containing medium seemed to be related to a reduction in the amount of cell-assoc iated DDT.