Fl. Baker et al., CELL-PROLIFERATION KINETICS OF NORMAL AND TUMOR-TISSUE IN-VITRO - QUIESCENT REPRODUCTIVE CELLS AND THE CYCLING REPRODUCTIVE FRACTION, Cell proliferation, 28(1), 1995, pp. 1-15
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.