CELL LOSS AND THE CONCEPT OF POTENTIAL DOUBLING TIME

The in vivo infusion of Bromodeoxyuridine (BrdUrd), followed by delaye d biopsy and bivariate DNA-BrdUrd flow cytometry, allows tile potentia l doubling time (T-pot) of human tumors to be estimated, According to Steel, the mathematical definition of T-pot is T-pot = ln 2/K-p, where K-p is the rate constant of cell production, All the operative formul as which allow the estimation of T-pot from flow cytometric data deriv e from this definition. Most authors, however identify the potential d oubling time as the doubling time that the same tell population would exhibit if cell loss were removed, We denote here as T-d(noloss) this quantity, Although these two definitions ate equivalent in the case of uniform random cell loss, we show, In the framework of Steel's theory of growing cell populations, that T-pot and T-d(noloss) become distin ct kinetic quantities when cell loss is not uniform, i,e,. when loss d ifferently affects the quiescent and the proliferative compartment. We discuss the validity of the two formulas currently used for the calcu lation of T-pot one based on LI and the other on the nu-function, in c onditions of non-uniform cell loss, Moreover, we propose two formulas for the estimation of the cycle time T-c, which require, in addition t o T-s and LII that a measure of the growth fraction be a available. (C ) 1997 Wiley-Liss, Inc.