A digital simulation of cell kinetics with application to L-1210 cells

Abstract A computer program has been developed to simulate a model of the normal cell cycle. This model postulates that the length of stay in each state, or “compartment”, of the cell cycle is a stochastic variable following a known probability distribution such as the normal, lognormal, or gamma. Other probability distributions could also be used. Normal cell proliferation can be simulated with the number of cells in each compartment shown for each time period. The model also permits the evaluation of different schedules of treatment on the proliferation of cells; each treatment is assumed to have a specified probability of killing a cell in the various states and this probability remains applicable for the period of activity of the drug. Simulation of the proliferation of L-1210 cells in mice has been accomplished with the program (see long write-up) and the mean and variability of time to death obtained corresponds very closely with the experimental results of Skipper, Schabel, and Wilcox (Cancer Chemotherapy Reports, 35: 1964) if gamma distributions are assumed for the length of stay in each state and if the logarithm of the number of cells required to kill an animal is assumed to follow an exponential distribution with a median of 1.5 × 10 9 .