Cell cycle controls in higher eukaryotic cells: Resting state or a prolonged G₁ period?

We express the viewpoint that control over cell growth in higher eukaryotes is achieved predominantly by regular transition of cells from proliferation to rest and vice versa as a result of coordinated interrelationship between intracellular growth inhibitors and extracellular growth factors. The resting state is considered as a special physiological state of a cell where the prereplicative reactions necessary for the onset of DNA synthesis are inhibited. Cells pass into a resting state at each successive cell cycle, with regard to the next cycle, once the threshold level of growth inhibitors has been attained. Cellular rest may thus initiate and proceed in parallel with conventional periods of the cell cycle but in a hidden way. Its termination strictly depends on the appropriate concentration of extracellular growth factors. In the absence of growth factors cells, after completing mitosis, pass into an overt state of rest metabolically different from any period of the cell cycle including G₁.