Concepts in Tumor Cell Biology

CONCEPTS IN TUMOR CELL BIOLOGY

The Normal Cell Cycle

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 Tumor Cell Cycle

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 T_c, is the time required to complete one cycle of cell growth and division. The T_c 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.