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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1974 Apr;71(4):1286–1290. doi: 10.1073/pnas.71.4.1286

A Restriction Point for Control of Normal Animal Cell Proliferation

Arthur B Pardee 1
PMCID: PMC388211  PMID: 4524638

Abstract

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 G1 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.

Keywords: growth control, cell survival, cancer

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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