Quantitative analysis of biological marker synthesis in tumor cell cycle.

ABSTRACT

A quantitative relationship between tumor cell number and biologic marker concentration has been investigated and characterized by the previously developed discrete-time kinetic model for the study of cell kinetics. Here, this model is further expanded to cope with both cell cycle kinetics and biologic marker synthesis. A synchronized tumor-cell population is examined to determine the time course of the synthesis of markers in relation to cell cycle. The DNA content distributions, measured by flow microfluorometry, are analyzed by use of the model, and the cell age distribution is extracted. The average marker content per cell in cell cycle is measured for each time sequence in synchronized cell populations. The model, incorporating the cell age distribution and the average marker content per cell in cell cycle, enables one to generate the marker content distribution, from which the cell number is estimated from the marker concentration. The model performance is further evaluated with Chinese hamster ovary cells, and their polyamine content and the total polyamine concentration during synchronization is calculated and related to the total cell number.