GAP JUNCTIONAL INTERCELLULAR COMMUNICATION IN MOUSE LUNG EPITHELIAL-CELL LINES - EFFECTS OF CELL-TRANSFORMATION AND TUMOR PROMOTERS

Gap junctional intercellular communication (GJIC) is reduced by neoplastic transformation and treatment with tumor promoters in many types of cells but few data exist for the lung. GJIC was therefore evaluated in non-transformed (C10) and transformed (E9, 82-132, and PCC4) mouse lung epithelial cell lines and in C10 cells treated with tumor promoters. GJIC was assessed by fluorescent dye microinjection (dye-coupling). Dye-coupling levels were highest in C10 cells (85-90% communicating cells) followed by 82-132 cells (40-50%), E9 cells (15-20%), and PCC4 cells (3-10%). Indirect immunofluorescent staining with anti-gap junction protein (connexin) antibodies revealed that C10 cells expressed gap junctions comprised of connexin43, but not connexin32 or connexin26. The tumor promoters, butylated hydroxytoluene (BHT), 12-O-tetradecanoylphorbol-13-acetate (TPA), and p,p'-dichlorodiphenyltrichloroethane (DDT), inhibited dye-coupling in CIO cells but phenobarbital (PB) did not. BHT promotes mouse lung tumor formation, PB does not, while the effects of TPA and DDT on lung tumor development have not been reported. These data indicate that cell transformation and certain tumor promoters reduce GJIC in mouse lung epithelial cells and demonstrate correlations between the in vitro inhibition of GJIC and lung tumor promotion.