HETEROGENEITY IN THE MOUSE EPIDERMAL-CELL CYCLE ANALYZED BY COMPUTER-SIMULATIONS

Different sets of cell kinetic data obtained over many years from hair less mouse epidermis have been simulated by a mathematical model inclu ding circadian variations. Simulating several independent sets of data with the same mathematical model strengthens the validity of the resu lts obtained. The data simulated in this investigation were all obtain ed with the experimental system in a state of natural synchrony. The d ata include cell cycle phase distributions measured by DNA flow cytome try of isolated epidermal basal cells, fractions of tritiated thymidin e ([H-3]TdR) labelled cells within the cell cycle phases measured by c ell sorting at intervals after [H-3]TdR pulse labelling, bivariate bro modeoxyuridine (BrdUrd)/DNA data from epidermal basal cells isolated a t intervals after pulse labelling with BrdUrd, mitotic rate and per ce nt labelled mitosis (PLM) data from histologic sections. The following main new findings were made from the simulations: the second PLM peak observed at about 35 h after pulse labelling is hardly influenced by circadian variations; the peak is mainly determined by persisting sync hrony of a rapidly cycling population with a G1-duration (T(G1)) of 20 h to 30 h; and there is a highly significant population of slowly cyc ling G1-cells (G1sigma). However, no significant circadian variations were found in the number of these cells.