THE GAP JUNCTIONAL INTERCELLULAR COMMUNICATION IS NO PREREQUISITE FORTHE STABILIZATION OF XENOBIOTIC-METABOLIZING ENZYME-ACTIVITIES IN PRIMARY RAT-LIVER PARENCHYMAL-CELLS IN-VITRO

In primary monocultures of adult rat liver parenchymal cells (PC), the activities of the xenobiotic metabolizing enzymes microsomal epoxide hydrolase (mEH(b)), soluble epoxide hydrolase (sEH), glutathione S-tra nsferases (GST), and phenolsulfotransferase (ST) were reduced after 7 d to values below 33% of the initial activities. Furthermore, the gap junctional intercellular communication (GJIC), measured after microinj ection by dye transfer, decreased from 90% on Day 1 to undetectable va lues after 5 d in monoculture. Co-culture of PC with nonparenchymal ra t liver epithelial cells (NEC) increased (98% on Day 1) and stabilized (82% on Day 7) the homotypic GJIC of PC. Additionally, most of the me asured xenobiotic metabolizing enzyme activities were well stabilized over 1 wk in co-culture. Because GJIC is one of several mechanisms pla ying an important role in cell differentiation, the importance of GJIC for the stabilization of xenobiotic metabolizing enzymes in PC was in vestigated. PC in monoculture were, therefore, treated with 2% dimethy l sulfoxide (DMSO), a differentiation promoting factor, and 1,1,1-tric hloro-2,2,-bis (p-chlorophenyl) ethane (DDT) (10 mu g/ml), a liver tum or promotor and inhibitor of GJIC, was given to co-cultures of PC with NEC. DMSO significantly stabilized (68% on Day 7), while DDT signific antly inhibited (8% on Day 7) homotypic GJIC of PC in the respective c ulture systems. In contrast, the activities of mEH(b), sEH, GST, and S T were not affected in the presence of DMSO or DDT. These results lead to the assumption that the differentiation parameters measured in thi s study (i.e., homotypic GJIC and the activities of xenobiotic metabol izing enzymes) are independently regulated in adult rat liver PC.