Inhibition of gap junctional intercellular communication by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rat hepatocytes

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent rodenthepatic tumor promoter. Unlike observations with the majorityof tumor promoting chemicals studied to date, most investigationshave failed to demonstrate down- regulation of gap junctionalintercellular communication (GJIC) in cultured cells by TCDD.The present study examined the effect of TCDD on GJIC in rathepatocytes in primary culture. At non-cytolethal doses TCDDinhibited GJIC In a time- (1, 4, 24 and 48 h) and concentration(1x10^–8–1x10^–14M)-dependent manner. This inhibitionoccurred within 4 h of treatment at doses of 1x10^–81x10–^–12MTCDD and persisted for up to 48 h, despite removal of TCDD.Treatment of rat hepatocytes with TCDD resulted in a decreasein hepatocyte connexin 32 mRNA, but had no apparent effect onconnexin 26 mRNA. Co-incubation of rat hepatocytes with TCDDand