Effect of in vivo exposure to the liver tumor promoters phenobarbital or DDT on the gap junctions of rat hepatocytes: a quantitative freeze-fracture analysis.
Some effects of in vivo exposure to the liver tumor promoters phenobarbital (PB) and p,p'-dichlorodiphenyltrichloroethane (DDT) on the gap junctions of hepatocytes were examined in a freeze-fracture analysis, using three groups of male ACI rats. Fifteen animals in Group 1 received a basal diet and were killed sequentially at 0, 2, 4, 6 and 8 weeks (three rats at each point) after the start of the experiment. Groups 2 (12 rats) and 3 (12 rats) were given 0.05% PB- and 0.05% DDT-containing diets respectively, and were also killed as Group 1. The frequency of hepatocyte gap junctions (per unit total membrane area) was always greater in PB-treated rats than in control rats at each killing point. In rats given DDT, the frequency of hepatocyte gap junctions was greater than in control rats at 2 and 4 weeks but was less than in control rats at 6 and 8 weeks. The average area of hepatocyte gap junctions in PB- and DDT-treated rats was significantly smaller than that in the corresponding control group (P less than 0.05-0.005). Small gap junctions within the meshwork of tight junctions were apparent only in the animals treated with PB or DDT. Promoter treatment also reduced the proportion of gap junctions per unit of hepatocyte membrane area. Furthermore, in comparison with controls, the size and distribution of gap junctional components were somewhat irregular in promoter-exposed livers. The structural changes in rat hepatocyte gap junctions observed upon in vivo exposure to PB or DDT may suggest an inhibitory effect of these agents on intercellular communication.
D000818:Animals; D003634:DDT; D005614:Freeze Fracturing; D007365:Intercellular Junctions / Q000187:drug effects* / Q000648:ultrastructure; D008099:Liver / Q000187:drug effects / Q000648:ultrastructure*; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D008854:Microscopy, Electron; D010634:Phenobarbital; D051381:Rats
D003634:DDT; D010634:Phenobarbital