Flow Cytokinetics
Studies of the proliferation characteristics of normal and malignant cells have been important to the biological characterizations of these cell types, to the elucidation of the biochemical mechanisms involved in cell replication, to understanding the mechanisms of action of drugs and radiation, and to the design of more effective cancer therapy strategies. The immediate experimental goal of these studies is usually to determine the rate at which cells change from one proliferative status to another; for example, the rate at which cells move from the G1-phase of the cell cycle to the S-phase, or the rate at which cells are recruited from a noncycling state (e.g., GO) into active proliferation. Alternatively, this information may be presented as the rate at which the cells traverse the various proliferative states or phases. At least four proliferative states have been identified: (1) actively proliferating and capable of extended proliferation (clonogenic), (2) actively proliferating but not clonogenic, (3) temporarily not proliferating (quiescent) but, upon stimulation, capable of proliferation and repopulation, and (4) not proliferating and nonclonogenic (doomed or fully differentiated). In addition, cells in any state can reside in at least four phases; G1, S, G2, and M (12 ).