Open AccessMathematical model analysis of mouse epidermal cell kinetics measured by bivariate DNA/anti‐bromodeoxyuridine flow cytometry and continuous [ 3 H]‐thymidine labelling
Author(s) -
Aarnæs E.,
Kirkhus B.,
Clausen O. P. F.
Publication year - 1990
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.1990.tb01134.x
Subject(s) - labelling , bromodeoxyuridine , thymidine , flow cytometry , population , biology , kinetics , cell cycle , bivariate analysis , dna synthesis , dna , cell , microbiology and biotechnology , biophysics , cell growth , biochemistry , physics , statistics , mathematics , demography , quantum mechanics , sociology
Abstract. In a previous study the epidermal cell kinetics of hairless mice were investigated with bivariate DNA/anti‐bromodeoxyuridine (BrdU) flow cytometry of isolated basal cells after BrdU pulse labelling. The results confirmed our previous observations of two kinetically distinct sub‐populations in the G 2 phase. However, the results also showed that almost all BrdU‐positive cells had left S phase 6–12 h after pulse labelling, contradicting our previous assumption of a distinct, slowly cycling, major sub‐population in S phase. The latter study was based on an experiment combining continuous tritiated thymidine ([ 3 H]TdR) labelling and cell sorting. The purpose of the present study was to use a mathematical model to analyse epidermal cell kinetics by simulating bivariate DNA/BrdU data in order to get more details about the kinetic organization and cell cycle parameter values. We also wanted to re‐evaluate our assumption of slowly cycling cells in S phase. The mathematical model shows a good fit to the experimental BrdU data initiated either at 08.00 hours or 20.00 hours. Simultaneously, it was also possible to obtain a good fit to our previous continuous labelling data without including a sub‐population of slowly cycling cells in S phase. This was achieved by improving the way in which the continuous [ 3 H]TdR labelling was simulated. The presence of two distinct sub‐populations in G 2 phase was confirmed and a similar kinetic organization with rapidly and slowly cycling cells in G 1 phase is suggested. The sizes of the slowly cycling fractions in G 1 and G 2 showed the same distinct circadian dependency. The model analysis indicates that a small fraction of BrdU labelled cells (3–5%) was arrested in G 2 phase due to BrdU toxicity. This is insignificant compared with the total number of labelled cells and has a negligible effect on the average cell cycle data. However, it comprises 1/3 to 1/2 of the BrdU positive G 2 cells after the pulse labelled cells have been distributed among the cell cycle compartments.