Dotto G P, Parada L F, Weinberg R A
Nature. 1985;318(6045):472-5. doi: 10.1038/318472a0.
Chemical carcinogenesis is a process involving multiple steps, as shown in several in vivo experimental systems. Two early steps have been well characterized: initiation, achieved by a single, subthreshold dose of a carcinogen, and promotion, induced by repetitive treatments with a non-carcinogenic tumour promoter. At the cellular level, establishment of the transformed phenotype is also a multi-step process and activation of several, independent genes appears to be required. Here we show that, like initiated cells, primary rat embryo fibroblasts (REFs) containing a ras but not a myc oncogene, are strongly and specifically stimulated to grow by tumour promoters. In the presence of these promoters, ras-containing REFs acquire the ability to overgrow normal cells in the monolayer and to form foci with 100% efficiency. Similar to the in vivo situation, promoter effects can be blocked by the concomitant application of retinoic acid.
化学致癌作用是一个涉及多个步骤的过程，这在多个体内实验系统中都有体现。两个早期步骤已得到充分表征：引发，由单一的亚阈值剂量致癌物实现；促进，由用非致癌性肿瘤促进剂进行重复处理诱导。在细胞水平上，转化表型的建立也是一个多步骤过程，似乎需要激活几个独立的基因。我们在此表明，与引发细胞一样，含有ras但不含myc癌基因的原代大鼠胚胎成纤维细胞（REFs）受到肿瘤促进剂的强烈且特异性刺激而生长。在这些促进剂存在的情况下，含有ras的REFs获得了在单层中过度生长正常细胞并以100%效率形成集落的能力。与体内情况类似，维甲酸的同时应用可阻断促进剂的作用。
