NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS BY ONCOGENES OR CARCINOGENS

激活的原癌基因家族ras、raf、jun、erbB-2(Neu)和 到目前为止，MYC与人类肺癌有关。人类 体外培养的支气管上皮细胞正被用来研究 这些特异的癌基因和生长调控基因在肺癌中的功能作用 癌变和肿瘤进展。癌基因转化细胞 含有DNA甲基化异常模式，类似于 在原发肺癌中发现。 由于肺癌的主要原因是吸烟， 最近不断的调查表明，苯并[a]芘或1，6- 二硝基芘将引起人支气管的肿瘤性转化 上皮细胞。转化的细胞形成转移性腺癌。 在裸鼠体内。这一新的体内/体外烟草癌模型-- 创世纪应该带来新的机械洞察力和机会 干预和化学预防。 一种人肝细胞癌变的体外模型正在研制中 发展起来的。SV40T永生化人肝细胞已被证明 代谢激活致癌物，包括黄曲霉毒素B1，来自3个不同的 化学课。

Five families of activated protooncogenes, ras, raf, jun, erbB-2 (neu) and myc have so far been associated with human bronchogenic carcinoma. Human bronchial epithelial cells in vitro are being used to investigate the functional role of these specific oncogenes and growth regulatory genes in carcinogenesis and tumor progression. The oncogene-transformed cells contained abnormal patterns of DNA methylation that were similar to those found in primary lung cancers. Since the major cause of bronchogenic carcinoma is tobacco smoke, continuing investigations have recently shown that benzo[a]pyrene or 1,6- dinitropyrene will cause neoplastic transformation of human bronchial epithelial cells. The transformed cells form metastatic adenocarcinomas in athymic nude mice. This new in vivo/in vitro model of tobacco carcino- genesis should lead to new mechanistic insights and opportunities for intervention and chemoprevention. An in vitro model of human hepatocellular carcinogenesis is being developed. SV40 T immortalized human hepatocytes have been shown to metabolically activate carcinogens including aflatoxin B1 from 3 different chemical classes.