Quantitative Description of Cell Cycle Kinetics Under Chemotherapy Utilizing Flow Cytometry

Abstract

A discrete time cell cycle kinetics model was developed to account for the effects of cytotoxic chemotherapy, particularly including the existence of cells destined to die. A model structure was determined from related experiments, leaving key parameter values undetermined. These values were found by determining the best least squares fit of the predicted to the observed DNA distribution data at a series of time intervals. The numerical methods included separable least squares, linear inequality constrained least squares and the Gauss-Newton method. This approach was applied to an experiment in which the [mouse] Ehrlich ascites tumor cells were given a single dose of bleomycin. The results included several different parameters, including the age response function and a time series of cell age and DNA distributions, which can be used as a basis for further treatment.