Effect of 1,1'-(2,2,2-trichloroethylidene)-bis(4-chlorobenzene) (DDT) on gap junctional intercellular communication and morphological transformation of Syrian hamster embryo cells.
The organochlorine insecticide 1,1'-(2,2,2-trichloroethylidene)bis(4-chlorobenzene) (DDT) did not induce or promote induction of morphological transformation in Syrian hamster embryo (SHE) cells, but it was a potent inhibitor of gap junctional intercellular communication (GJIC). The kinase inhibitor staurosporine did not affect DDT induced inhibition of GJIC, although it has been shown to decrease the inhibitory effect of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on GJIC. In addition, pretreatment with TPA made the cells refractory to further TPA induced inhibition of GJIC, while they remained sensitive to DDT. Thus, DDT and 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 (EC50 value) resulted in a slight recovery of GJIC following the initial inhibition. This recovery was not accompanied by the cells becoming refractory to further DDT induced inhibition 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-associated DDT.
Roseng
L E
LE
Laboratory for Environmental and Occupational Cancer, Norwegian Radium Hospital, Oslo.
Rivedal
E
E
Skaare
J U
JU
Sanner
T
T
D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002478:Cells, Cultured; D006224:Cricetinae; D003634:DDT / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects*; D008647:Mesocricetus
D003634:DDT