Kuroki T, Huh N H
Department of Cancer Cell Research, University of Tokyo.
Jpn J Cancer Res. 1993 Nov;84(11):1091-100. doi: 10.1111/j.1349-7006.1993.tb02806.x.
Transformation of human cells, both induced and spontaneous, is an extremely rare event, whereas rodent cells are relatively easily transformed when treated with a single carcinogenic agent. The present review addresses the question of why human cells are resistant to malignant transformation in vitro. To facilitate understanding of the problem, the process of transformation is divided operationally into two phases, i.e. phase I, immortalization; and phase II, malignant transformation. In human cells, one-phase transformation, i.e., the consecutive occurrence of phases I and II due to the action of a single carcinogenic agent, is observed only rarely. Once human cells are immortalized, however, malignant transformation by chemical carcinogens or oncogenes proceeds, suggesting that for human cells, phase I immortalization is a prerequisite for such transformation to take place. To date, about 20 papers have been published describing protocols for the two-phase transformation of a variety of human epithelial cells and fibroblasts. In most experiments, SV40, human papilloma viruses and their transforming genes are utilized for induction of phase I (immortalization) followed by the use of chemical carcinogens or activated oncogenes for induction of phase II (malignant transformation). Possible mechanisms that would render human cells refractory to transformation are discussed below.
人类细胞的转化，无论是诱导性的还是自发性的，都是极其罕见的事件，而啮齿动物细胞在用单一致癌剂处理时相对容易转化。本综述探讨了人类细胞为何在体外对恶性转化具有抗性这一问题。为便于理解该问题，将转化过程在操作上分为两个阶段，即第一阶段，永生化；以及第二阶段，恶性转化。在人类细胞中，单阶段转化，即由于单一致癌剂的作用而连续发生第一阶段和第二阶段的情况，仅很少被观察到。然而，一旦人类细胞永生化，化学致癌物或癌基因引发的恶性转化就会进行，这表明对于人类细胞而言，第一阶段的永生化是发生这种转化的先决条件。迄今为止，已发表了约20篇论文，描述了多种人类上皮细胞和成纤维细胞两阶段转化的方案。在大多数实验中，SV40、人乳头瘤病毒及其转化基因被用于诱导第一阶段（永生化），随后使用化学致癌物或激活的癌基因来诱导第二阶段（恶性转化）。下文将讨论使人类细胞难以发生转化的可能机制。
