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Proc Natl Acad Sci U S A. 1974 Apr;71(4):1286-90. doi: 10.1073/pnas.71.4.1286.
This paper provides evidence that normal animal cells possess a unique regulatory mechanism to shift them between proliferative and quiescent states. Cells cease to increase in number under a diversity of suboptimal nutritional conditions, whereas a uniformity of metabolic changes follows these nutritional shifts. Evidence is given here that cells are put into the same quiescent state by each of these diverse blocks to proliferation and that cells escape at the same point in G(1) of the cell cycle when nutrition is restored. The name restriction point is proposed for the specific time in the cell cycle at which this critical release event occurs. The restriction point control is proposed to permit normal cells to retain viability by a shift to a minimal metabolism upon differentiation in vivo and in vitro when conditions are suboptimal for growth. Malignant cells are proposed to have lost their restriction point control. Hence, under very adverse conditions, as in the presence of antitumor agents, they stop randomly in their division cycle and die.
本文提供的证据表明，正常动物细胞拥有一种独特的调节机制，可使其在增殖和静止状态之间转换。在多种次优营养条件下，细胞数量不再增加，而这些营养变化会伴随代谢变化的一致性。此处有证据表明，这些不同的增殖阻滞都会使细胞进入相同的静止状态，并且当营养恢复时，细胞会在细胞周期的G(1)期的同一点逃脱。对于细胞周期中发生这一关键释放事件的特定时间，我们提出了“限制点”这一名称。我们提出，限制点控制可使正常细胞在体内和体外分化时，在生长条件次优的情况下通过转变为最低代谢水平来维持活力。我们认为恶性细胞已经失去了它们的限制点控制。因此，在非常不利的条件下，如存在抗肿瘤药物时，它们会在分裂周期中随机停止并死亡。
