CONCEPTS IN TUMOR CELL BIOLOGY
The normal cell cycle consists of a definable sequence of events that characterize the growth and division of cells and can be observed by morphological and biochemical means. The cell cycle is depicted in Fig. 55.1. Two of the four phases of the cell cycle can be studied directly: the M-phase, or mitosis, is easily visible using light mi-croscopy because of chromosomal condensation, spin-dle formation, and cell division. The S-phase is the pe-riod of DNA synthesis and is observed by measuring the incorporation of tritiated thymidine into cell nuclei.
The mitotic index is the fraction or percentage of cells in mitosis within a given cell population. The thymidine labeling index is the fraction of cells incorpo-rating radioactive thymidine. They represent cells in M-phase and S-phase and define the proliferative charac-teristics of normal and tumor cells.
The duration of the S-phase in human tumors is 10 to 20 hours. This period is followed by the G2-phase, or period of preparation for mitosis, in which cells contain a tetraploid number of chromosomes. The G2-phase lasts only 1 to 3 hours for most cell types, with mitosis itself lasting approximately 1 hour. The two daughter cells then enter the G1-phase, whose duration varies from several hours to days. The G1-phase also can give rise to a resting state, termed G0, in which cells are relatively inactive metabolically and are resistant to most chemotherapeutic drugs.
The generation time, or Tc, is the time required to complete one cycle of cell growth and division. The Tc will vary with the duration of the G1-phase. The factors that influence daughter cells to enter the G0, or resting stage, are not well understood. The ability to cause such resting cells to reenter the cell cycle would be quite use-ful, since proliferating cells generally are more sensitive to chemotherapy than are resting cells.
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