GAP JUNCTIONAL INTERCELLULAR COMMUNICATION AND CONNEXIN EXPRESSION INNORMAL AND SV 40-TRANSFORMED HUMAN LIVER-CELLS IN-VITRO

The gap junction intercellular communication (GJIC) capacity of two no rmal human liver-derived epithelial cell strains and their SV40 large T oncogene-transformed counterparts was examined. In homologous cultur es the GJIC capacity of the transformed cells was considerably less th an the parental cells. In heterologous cultures, transformed cells app eared to be able to form GJIC channels with normal cells. Only non-tra nsformed cells expressed connexin (cx) 43 gene and cx 26 or cx 32 tran scripts were not detectable in any cell strains tested. When GJIC was assayed in the presence of the phorbol ester tumour promoter 12-O-tetr adecanoylphorbol-13-acetate (TPA), all four strains showed a marked se nsitivity to TPA in inhibitory activity at 1-10 ng/ml. In contrast to a rat liver epithelial cell line, this effect of TPA did not appear to become refractory even after 24 h exposure. These studies demonstrate that GJIC of human liver cells in culture can be decreased by viral o ncogene and tumour promoter action. Such disturbance may be an importa nt component of the carcinogenic activity of these agents.