THE DISCRETE–TIME KINETIC MODEL ANALYSIS OF DNA CONTENT DISTRIBUTIONS IN EXPERIMENTAL TUMOUR CELLS

Abstract

A method was developed to analyse and characterize FMF measurements of DNA content distribution, utilizing the discrete time kinetic (DTK) model for cell kinetics analysis. The DTK model determines the time sequence of the cell age distribution during the proliferation of a tumor cell population and simulates the distribution pattern of the DNA content of cells in each age compartment of the cell cycle. The cells in one age compartment are distributed and spread into several compartments of the DNA content distribution to allow for different rates of DNA synthesis and instrument dispersion effects. It is assumed that the DNA content of cells in each age compartment has a Gaussian distribution. Thus, for a given cell age distribution the DNA content distribution depends on two parameters of the cells in each age compartment: the average DNA content and its coefficient of variation. As the DTK model generates the best fit DNA content distribution to the FMF measurement data, it enables one to estimate specific values of these two parameters in each stage of the cell cycle and to determine the fraction of cells in each cycle phase. The method was utilized to fit FMf measurements of DNA content distributions and to analyse their relationship tothe cell kinetic parameters, namely cell loss rate, cell cycle times and grwoth graction of exponentially growing Chinese hamster ovary cells in vitro and, also, with a wide range of coeffficients of variation, of the L1210 ascites tumour during the growth period.