CELL-CYCLE ANALYSIS BY THE RELATIVE MOVEMENT APPROACH - EFFECT OF VARIABILITY ACROSS S-PHASE OF DNA-SYNTHESIS RATE

Cell populations pulse-labelled with BrdUrd, and sampled at increasing times after the pulse, yield DNA-BrdUrd distributions from which the relative movement (RM) and the depletion function (DF) of labelled, un divided cells can be calculated. In this paper we present an extension of the equation for the time course of RM, given by White and Meistri ch (Cytometry 1986, 7, 486-490), to the case in which the rate of DNA synthesis changes across S-phase. Some modalities of cell loss were al so considered. Computer simulations showed that different patterns of DNA synthesis rate across S-phase can result in appreciably different RM curves. An analytical expression of the RM curve, in which the vari ability across S-phase of the rate of DNA synthesis is accounted for b y only one parameter, was proposed. This expression was used for the s imultaneous fitting of time sequences of RM and DF data of U937 cells, in order to estimate the phase transit times T-S and T-G2+m, and the potential doubling time T-pot. The use of the extended model gave bett er results than those obtained under the assumption of constant rate o f DNA synthesis across S-phase.