Sasajima K, Willey J C, Banks-Schlegel S P, Harris C C
J Natl Cancer Inst. 1987 Mar;78(3):419-23.
The acute effects of 12-O-tetradecanoylphorbol-13-acetate [(TPA) CAS: 56937-68-9], T-2 toxin (CAS: 21259-20-1), capsaicin (CAS: 404-86-4), cigarette smoke condensate (CSC), and ethanol (CAS: 3807-77-0) were examined in secondary cultured human esophageal epithelial cells in serum-free LHC-8 medium. Effects were evaluated by morphology and measurement of clonal growth rate (population doublings per day), cross-linked envelope (CLE) formation, and the enzymatic activities of ornithine decarboxylase (ODC) and plasminogen activator (PA). All compounds tested were inhibitory to clonal growth; concentrations causing 50% growth inhibition were estimated as 10 nM TPA, 6 nM T-2 toxin, 40 microM capsaicin, 8 micrograms CSC/ml, 540 mM ethanol, and 0.8 microgram CSC/ml with 220 mM ethanol. None of the compounds tested induced CLE formation, although calcium ionophore (A23187) could induce CLE in at least 60% of the cells. TPA (10 and 100 nM) decreased the ODC activity of cells, and capsaicin (100 microM) induced ODC by 220%. TPA (1-100 nM) and capsaicin (100 microM) also induced PA activity. Slight increases in ODC activity by CSC (10 micrograms/ml), CSC (1 microgram/ml) with ethanol, and T-2 toxin (1 nM) were observed, but PA activity was not affected by these compounds. The results indicated that the response of human esophageal epithelial cells to TPA is both similar to and different from that reported for human epidermal and bronchial cells in vitro. Enhancement of PA activity and decrease in ODC by TPA are found in all three human epithelial cell types. However, these changes are not associated in esophageal cells with increased CLE formation as reported in studies with the use of bronchial and epidermal epithelial cells. The results from these acute studies provide the basis for designing in vitro carcinogenesis investigations using these agents.
在无血清的LHC - 8培养基中，对二次培养的人食管上皮细胞检测了12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯[（TPA），化学物质登记号：56937 - 68 - 9]、T - 2毒素（化学物质登记号：21259 - 20 - 1）、辣椒素（化学物质登记号：404 - 86 - 4）、香烟烟雾冷凝物（CSC）和乙醇（化学物质登记号：3807 - 77 - 0）的急性效应。通过形态学以及克隆生长速率（每天的群体倍增数）、交联包膜（CLE）形成的测定，以及鸟氨酸脱羧酶（ODC）和纤溶酶原激活剂（PA）的酶活性评估效应。所有测试的化合物均抑制克隆生长；导致50%生长抑制的浓度估计为10 nM TPA、6 nM T - 2毒素、40 μM辣椒素、8 μg CSC/ml、540 mM乙醇，以及0.8 μg CSC/ml与220 mM乙醇。尽管钙离子载体（A23187）可在至少60%的细胞中诱导CLE形成，但所测试的化合物均未诱导CLE形成。TPA（10和100 nM）降低细胞的ODC活性，而辣椒素（100 μM）使ODC诱导增加220%。TPA（1 - 100 nM）和辣椒素（100 μM）也诱导PA活性。观察到CSC（10 μg/ml）、CSC（1 μg/ml）与乙醇以及T - 2毒素（1 nM）使ODC活性略有增加，但这些化合物不影响PA活性。结果表明，人食管上皮细胞对TPA的反应与体外报道的人表皮和支气管细胞的反应既有相似之处又有不同之处。在所有三种人上皮细胞类型中均发现TPA增强PA活性并降低ODC。然而，如在支气管和表皮上皮细胞研究中所报道的，在食管细胞中这些变化与CLE形成增加无关。这些急性研究的结果为使用这些试剂设计体外致癌研究提供了基础。
