Intercellular communication in primary cultures of putative preneoplastic and 'normal' hepatocytes

Gap junctional intercellular communication (IC) was studied in gamma-glutamyltranspeptidase (gamma-GT)-positive and -negative hepatocytes isolated from carcinogen-treated rats. Putative preneoplastic gamma-GT-positive hepatocytes were visualized in monolayer cultures by indirect immunofluorescence using anti-gamma-GT-antibodies. IC was evaluated by studying dye coupling of the cells. gamma-GT-positive hepatocytes showed a significantly lower dye coupling than did gamma-GT-negative liver cells. Spread of the dye Lucifer Yellow CH to neighboring cells was decreased further by the tumor-promoting chemical phenobarbital in both cell types in vitro. Also treatment in vivo with the barbiturate significantly reduced dye coupling of hepatocytes. The findings suggest that as a result of their decreased ability to communicate, preneoplastic hepatocytes may escape from growth control and differentiation signals given out by surrounding 'normal' cells.