Cell-cycle analysis of perturbed cell populations: computer simulation of sequential DNA distributions.

A mathematical model is presented that permits simulation of a time sequence of DNA distributions with a single set of cell-cycle parameters. The method is particularly suited to the quantitative analysis of sets of sequential DNA distributions from perturbed cell populations. The model permits determination of the durations and associated dispersions of the phases of the cell cycle as well as the point in the cell cycle at which the perturbing agent exerts its effect. The mathematical details of the simulation technique are presented, and the technique is applied to the analysis of DNA distributions from perturbed cell populations. Three cell populations are modeled: CHO-line cells released from a block at the interface of the G1-and S-phases, 3T3 cells released from a G1-phase block produced by serum starvation, and S49 mouse lymphoma cells responding to a block in the G1-phage produced by N6,02'-dibutyryl adenosine 3':5'-cyclic monophosphate (Bt2cAMP).