Haas I, Koldovsky P, Ganzer U
Department of Otorhinolaryngology, Head and Neck Surgery, Heinrich Heine University, Düsseldorf, Germany.
Eur Arch Otorhinolaryngol. 1996;253(7):405-10. doi: 10.1007/BF00168492.
As a continuation of previous experiments introducing an extracorporeal model for transformation of human respiratory epithelium that might be able to mimic a spontaneously occurring malignant tumor, we prepared organ cultures from tracheal specimens and exposed them repeatedly to chemical carcinogens, using benzo(a)pyrene and methylnitronitrosoguanine for 6 weeks. We then tried to select possibly initiated cells by subsequent co-cultivation with autologous isotopic fibroblasts for 2 years. Nontreated controls were maintained from the same specimens and cultured in the same manner. By this technique we selected from specimen La24 three long-living cell lines with varying morphology and an antigenic pattern indicating dedifferentiation. The cells expressed simultaneously a panel of cytokeratins, vimentin and neuroectodermal antigens. Transplantation of these cell lines under the subrenal capsule of athymic mice resulted in tumorlike nodules of limited size. Success rate was dependent on time of previous in vitro culture and carcinogen treatment. None of the lines produced invasive or metastasizing tumors.
作为先前实验的延续，我们引入了一种体外模型来模拟人类呼吸道上皮细胞向可能自发形成恶性肿瘤的转化过程。我们从气管标本中制备了器官培养物，并使用苯并(a)芘和甲基硝基亚硝基胍，将其反复暴露于化学致癌物中6周。然后，我们通过随后与自体同位素成纤维细胞共培养2年，试图筛选出可能已启动转化的细胞。从相同标本中选取未处理的对照组，并以相同方式进行培养。通过这种技术，我们从标本La24中筛选出了三个具有不同形态和表明去分化的抗原模式的长寿细胞系。这些细胞同时表达一组细胞角蛋白、波形蛋白和神经外胚层抗原。将这些细胞系移植到无胸腺小鼠的肾包膜下，形成了大小有限的肿瘤样结节。成功率取决于先前体外培养和致癌物处理的时间。这些细胞系均未产生侵袭性或转移性肿瘤。
