CELL-PROLIFERATION KINETICS OF NORMAL AND TUMOR-TISSUE IN-VITRO - QUIESCENT REPRODUCTIVE CELLS AND THE CYCLING REPRODUCTIVE FRACTION

Current methods for measuring the cell kinetics of human tumours are m ade and interpreted within the context of a simplistic two compartment model for cell proliferation, consisting of cells that are cycling an d those that are not. It is now recognized that the non-cycling compar tment of many tumours is heterogeneous, composed of non-reproductive e nd-stage cells and reproductive cells that are dormant/quiescent. We h ave developed an in vitro analysis that distinguishes for the first ti me quiescent reproductive cells from non-reproductive end-stage cells and have integrated this analysis with monolayer clonogenic and suicid e assays to simultaneously quantitate the duration of the cell cycle a nd reproductive cells that are: cycling, quiescent, clonogenic, and no n-reproductive end-stage cells. We have defined a new parameter, the C ycling Reproductive Fraction (CRF), which is the cycling cell populati on referenced specifically to the reproductive cell population. Measur ements of CRF from 72 tumour biopsies and from 5 normal foreskins show ed that CRF approached 100% in some tumours; however, CRF showed near normal values (< 1%) in others suggesting that cell cycle control may be maintained in some tumours. Because of CRF's improved specificity, we believe that CRF may enhance classification, prognostication, and t he optimization and prediction of response to chemotherapy.