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The Relationship of the Cell Cycle to Tumor Growth and Control of Cell Division: A Review

( Department of Pathology, Northwestern University Medical School, Chicago, Illinois)

Metabolic activities of cells during interphase can be studied by high-resolution autoradiography with tritium-labeled precursors of nucleic acids and proteins. After completion of mitosis, offspring of the parent cell may divide again, or may differentiate and die without further division. Dividing cells go through a series of metabolic changes which constitute the cell cycle. The cell cycle is subdivided into 4 distinct phases: (a) a postmitotic phase called G₁, during which the cell synthesizes ribonucleic acid (RNA) and proteins; (b) an S phase, during which the amount of deoxyribonuleic acid (DNA) is duplicated while protein and RNA syntheses continue; (c) a postsynthetic phase, called G₂, characterized by no net synthesis of DNA and continued RNA and protein synthesis as in postmitotic phase; and (d) mitosis, extending from beginning of prophase to completion of telophase during which there is no DNA synthesis, protein synthesis is reduced to a minimum, and RNA synthesis is limited to early prophase and late telophase. The length of the cell cycle and its 4 phases can be obtained by appropriate experimentation with labeled thymidine, a precursor of DNA, and high-resolution autoradiography. Although the length of the cell cycle varies in different kinds of cells, it is shorter in certain cells of the adult animal than in some of the fastest growing tumors. Tumor growth, therefore, must involve other kinetic parameters besides speed of cell proliferation. Since these parameters are related to control of cell division and since a cell in DNA synthesis is generally a cell that has already taken the decision to divide, the various factors involved in initiation of DNA biosynthesis are of particular interest in any attempt to explain the mechanism of tumor growth. It is possible that the initiation of DNA biosynthesis may involve DNA itself, and may be mediated through synthesis of specific RNA and enzymes.

¹ USPHS Research Career Development awardee (5-K3-GM-15, 465-05).

Received 9/ 2/64. Revised 1/15/65.

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