Acute effects of 12-Otetradecanoylphorbol-13-acetate, teleocidin B, or 2,3,7,8-tetrachlorodibenzo-p-dioxin on cultured normal human bronchial epithelial cells

Effects of teleoddin B, 12-O-tetradecanoylphorboi-13-acetate(TPA), phorbol, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and2,7-dichlorodibenzo-p-dioxin (DCDD) on normal human bronchialepithelial cell cultures were assessed by quantitation of cellularmorphology, clonal growth (population doublings per day), cross-linkedenvelope (CLE) formation and the enzymatic activities of arylhydrocarbon hydroxylase (AHH), ornithine decarboxylase (ODC)and plasminogen activator (PA). Toxicity was assessed by clonalgrowth assays. Teleocidin B and TPA had similar effects on growth,morphology and enzyme activities. When the cells were incubatedwith TPA or teleocidin B at concentrations of 1–100 nMfor 6 h, RNA synthesis was unaffected, but DNA synthesis decreasedand squamous differentiation, marked by an increase in cellsurface area and cross-linked envelope formation, was increased.TPA and teleocidin B also increased ODC activity in LHC-0 medium(a maintenance medium without epidermal growth factor) but causeda decrease of ODC activity in LHC-4 (a growth medium containingepidermal growth factor). Finally, TPA and teleocidin B eachcaused an increase of PA and a decrease of AHH activities inboth media. Phorbol, a non-promoting analogue of TPA, had noeffect on growth, morphology or biochemical assays. TCDD (100nM) caused a 15% decrease in cell growth when cells were incubatedin LHC-4, and this was accompanied by an increase in cell surfacearea, PA activity, and CLE formation. TCDD caused an increasein AHH and ODC activities when the cells were incubated in eitherLHC-0 or LHC-4 medium. DCDD did not alter cell growth, and itsmorphological and biochemical effects were similar to thoseof TCDD although less marked. In conclusion, results reportedhere are consistent with the hypothesis that an important propertyof some tumor promoters is their ability to induce terminaldifferentiation in normal, non-initiated epithelial cells.