Variation of cell kinetic parameters in relation to the growth rate of the Ehrlich ascites tumor.

A multicompartmental model of the cell cycle and proliferation kinetics was used to analyse the time-course behavior of the cell cycle time, the growth fraction, and the cell loss rate during Ehrlich ascites tumor growth. The growth rate of Ehrlich ascites tumor cells as the tumor aged was significantly influenced by change in the cell cycle time.

Analysis of the effects of antitumor drugs on cell cycle kinetics.

A cell cycle stage-specific multicompartmental model has been developed and used to investigate the effects of antitumor drugs on the proliferation of tumors. The drug effects simultaneously considered are (a) non-cycle-specific killing and cycle stage-specific killing of cells, (b) progression delay of cells through the cell cycle phases which may bring about an accumulation of cells in various phases of the cell cycle, and (c) prolongation of cell cycle times. These effects are analyzed in terms of possible variations in the behavior of cell kinetic parameters (namely, cell cycle times, cell loss rate, and growth fraction) and are implemented in the model specifying proper functional forms for the parameters. The time-course of drug distribution in a tumor-host system is also described by a two-compartment model and the factors affecting drug action are quantitatively formulated as a function of drug concentration. Simulation is carried out to examine the effects of BCNU, cytosine arabinoside, and methotrexate on the cell cycle and proliferation kinetics of L1210 leukemia, and the results of the simulation compare favorably with available experimental data. Also discussed are the sensitivity of drug effects to variation in dosage schedule and the different nodes of drug actions exerted on each cell cycle phase.