Dynamic Rendering of the Heterogeneous Cell Response to Anticancer Treatments
Figure 6
Checkpoint activities in the best-fit final model, as a function of the dose, in subsequent generations.
(A), G1- and G2M-block probability (i.e. the fraction of cell intercepted and blocked at G1 and G2M checkpoints among cycling cells entering these phases) in irradiated cells (gen0) and their descendants (block probabilities in gen1 and gen2 were not distinguishable). (B) Outcome of G1-blocked cells, showing the percentages of cells that re-enter the cycle, die or remain blocked at 72 h in the indicated generations. (C) Outcome of G2M-blocked cells, symbols as in panels B. (D) Dose-dependence of the delay in phase S (fractional reduction of DNA synthesis rate) in gen0 and gen1. Data fit required a distinction between the delay of cells irradiated in S phase (BrdU+) and in G1/G2M (BrdU−) in gen0. No delay was found in gen2. (E) Polyploidization rate, as the percentage of cells that re-fused in gen1 and gen2. Error bars indicate 95% confidence intervals for parameter and derived quantities (e.g. fraction of blocked cells), calculated by fitting 1000 synthetic datasets generated by a Monte Carlo procedure (see Uncertainty Analysis in supplementary Text S4).