Acute effects of 12-O-tetradecanoylphorbol-13-acetate, teleocidin B, or 2,3,7,8-tetrachlorodibenzo-p-dioxin on cultured normal human bronchial epithelial cells.
Effects of teleocidin B, 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,7-dichlorodibenzo-p-dioxin (DCDD) on normal human bronchial epithelial cell cultures were assessed by quantitation of cellular morphology, clonal growth (population doublings per day), cross-linked envelope (CLE) formation and the enzymatic activities of aryl hydrocarbon hydroxylase (AHH), ornithine decarboxylase (ODC) and plasminogen activator (PA). Toxicity was assessed by clonal growth assays. Teleocidin B and TPA had similar effects on growth, morphology and enzyme activities. When the cells were incubated with TPA or teleocidin B at concentrations of 1-100 nM for 6 h, RNA synthesis was unaffected, but DNA synthesis decreased and squamous differentiation, marked by an increase in cell surface 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 caused a decrease of ODC activity in LHC-4 (a growth medium containing epidermal growth factor). Finally, TPA and teleocidin B each caused an increase of PA and a decrease of AHH activities in both media. Phorbol, a non-promoting analogue of TPA, had no effect on growth, morphology or biochemical assays. TCDD (100 nM) caused a 15% decrease in cell growth when cells were incubated in LHC-4, and this was accompanied by an increase in cell surface area, PA activity, and CLE formation. TCDD caused an increase in AHH and ODC activities when the cells were incubated in either LHC-0 or LHC-4 medium. DCDD did not alter cell growth, and its morphological and biochemical effects were similar to those of TCDD although less marked. In conclusion, results reported here are consistent with the hypothesis that an important property of some tumor promoters is their ability to induce terminal differentiation in normal, non-initiated epithelial cells.
D000470:Alkaloids / Q000633:toxicity*; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004147:Dioxins / Q000633:toxicity*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008235:Lyngbya Toxins; D010704:Phorbols / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D014158:Transcription, Genetic / Q000187:drug effects
D000470:Alkaloids; D002273:Carcinogens; D004147:Dioxins; D008235:Lyngbya Toxins; D010704:Phorbols; D000072317:Polychlorinated Dibenzodioxins; C022176:teleocidins; D013755:Tetradecanoylphorbol Acetate