ALTERED FUNCTION, LOCALIZATION AND PHOSPHORYLATION OF GAP-JUNCTIONS IN RAT-LIVER EPITHELIAL, IAR-20, CELLS AFTER TREATMENT WITH PCBS OR TCDD

Three different PCB-congeners 3,4,5,3',4'-pentachlorobiphenyl (IUPAC n o. 126), 2,4,5,2',4',5'-hexachlorobiphenyl (IUPAC no. 153) and 2,4,5,3 ',4'-pentachlorobiphenyl (IUPAC no. 118) were investigated for possibl e structure-activity relationships in altering gap junction intercellu lar proteins. All tested PCB-congeners and TCDD decreased the gap junc tional intercellular communication in IAR 20 cells, but al different t reatment periods, suggesting different modes of action. The presence o f the Cx43-P-2 band, a phosphorylated isoform of Cx43, was associated with a functional communication. A reduced Cx43 mRNA level was noted a fter 48 h of exposure with PCB 126, PCB 118 and TCDD. In summary, the non dioxin-like PCB 153 can decrease gap junctional intercellular comm unication rapidly by reducing the phosphorylated isoform of Cx43, wher eas the dioxin-like PCB 126 and TCDD reduce the communication slowly b y decreasing the mRNA level of Cx43, resulting in a reduced Cx43 prote in level (which includes the P-2-band). The mixed inducing PCB-congene r, PCB 118, can act both as the dioxin-like and the non dioxin-like PC Bs in gap junction regulation. (C) 1997 Elsevier Science B.V.