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 no. 126), 2,4,5,2′,4′,5′-hexachlorobiphenyl (IUPAC no. 153) and 2,4,5,3′,4′-pentachlorobiphenyl (IUPAC no. 118) were investigated for possible structure–activity relationships in altering gap junction intercellular proteins. All tested PCB-congeners and TCDD decreased the gap junctional intercellular communication in IAR 20 cells, but at different treatment periods, suggesting different modes of action. The presence of the Cx43-P 2 band, a phosphorylated isoform of Cx43, was associated with a functional communication. A reduced Cx43 mRNA level was noted after 48 h of exposure with PCB 126, PCB 118 and TCDD. In summary, the non dioxin-like PCB 153 can decrease gap junctional intercellular communication rapidly by reducing the phosphorylated isoform of Cx43, whereas the dioxin-like PCB 126 and TCDD reduce the communication slowly by decreasing the mRNA level of Cx43, resulting in a reduced Cx43 protein level (which includes the P 2-band). The mixed inducing PCB-congener, PCB 118, can act both as the dioxin-like and the non dioxin-like PCBs in gap junction regulation.