Genomic 5-methyldeoxycytidine decreases associated with the induction of squamous differentiation in cultured normal human bronchial epithelial cells.

The terminal squamous differentiation of epithelial cells involves a number of cellular changes. However, the mechanisms underlying this differentiation process are unknown. The present study demonstrates that 5-azacytidine, 12-O-tetradecanoylphorbol-13-acetate (TPA) and type beta-transforming growth factor (TGF-beta) significantly diminish the genomic 5-methyldeoxycytidine (5mdC) content of normal human bronchial epithelial cells concomitantly with the induction of squamous differentiation. 5-Azacytidine or TPA, but not type beta-transforming growth factor, also initiated decreases in the genomic 5mdC content of differentiation nonresponsive human tumor A549 cells. These effects of TPA or type beta-transforming growth factor occurred at concentrations of 1 nM and 1.2 pM, respectively, which were approximately one tenth of kd values of their specific receptors. Therefore, the decreases in genomic 5mdC induced by these agents were probably mediated, directly or indirectly, by receptor--ligand interactions.