Skip to main content
Biophysical Journal logoLink to Biophysical Journal
. 1974 Aug;14(8):607–624. doi: 10.1016/S0006-3495(74)85938-2

Kinetic Cell-Cycle Analysis of a Cultured Mammalian Cell Population

BV Bronk, GJ Dienes, R Schindler, JR Gautschi
PMCID: PMC1334555  PMID: 4212118

Abstract

The parameters of the cell cycle are analyzed in terms of the stochastic theory of cell proliferation for a murine mastocytoma line. The cells were grown in suspension culture under steady-state conditions in a chemostat. Initial estimates of the parameters from synchronous growth indicate that agreement of the data with the model is obtained only if the model is modified to include an initial proliferating fraction of less than 100%, and a cell loss continuing throughout the course of the experiment. The analysis verifies that the modified theory adequately describes the data, and that similar parameters are obtained from both desynchronization and percent labeled mitosis experiments. The average cycle time from 10 desynchronization experiments was 8.24 ± 0.52 h with a cellular standard deviation of 1.28 ± 0.18. The combined parameter obtained by dividing the cellular standard deviation by the cycle time is shown to be a useful measure of biological variability well defined over many different experiments. The rate constant for cell loss is about 0.009 which gives an 8% cell loss per cycle. The cell loss is sufficient to account for the apparent deficit in initially proliferating cells. The initial distribution of the synchronous cells is qualitatively examined and is found to be peaked late in G1 or early in S.

Full text

PDF
608

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brockwell P. J., Trucco E. On the decomposition by generations of the PLM-function. J Theor Biol. 1970 Jan;26(1):149–179. doi: 10.1016/s0022-5193(70)80037-6. [DOI] [PubMed] [Google Scholar]
  2. Bronk B. V., Dienes G. J., Paskin A. The stochastic theory of cell proliferation. Biophys J. 1968 Nov;8(11):1353–1398. doi: 10.1016/S0006-3495(68)86561-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bronk B. V. On radioactive labeling of proliferating cells: the graph of labeled mitosis. J Theor Biol. 1969 Mar;22(3):468–492. doi: 10.1016/0022-5193(69)90016-2. [DOI] [PubMed] [Google Scholar]
  4. Eaves G. The rotating Fourier's ring. An alternative model for cell kinetic studies. Biophys J. 1972 Nov;12(11):1415–1428. doi: 10.1016/S0006-3495(72)86172-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gautschi J. R., Schindler R., Hürni C. Studies on the division cycle of mammalian cells. V. Modifications of time parameters by different steady-state culture conditions. J Cell Biol. 1971 Dec;51(3):653–663. doi: 10.1083/jcb.51.3.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hirsch H. R., Engelberg J. Decay of cell synchronization: solutions of the cell-growth equation. Bull Math Biophys. 1966 Sep;28(3):391–409. doi: 10.1007/BF02476821. [DOI] [PubMed] [Google Scholar]
  7. Kubitschek H. E. The distribution of cell generation times. Cell Tissue Kinet. 1971 Mar;4(2):113–122. doi: 10.1111/j.1365-2184.1971.tb01522.x. [DOI] [PubMed] [Google Scholar]
  8. PAINTER R. B., DREW R. M. Studies on deoxyribonucleic acid metabolism in human cancer cell cultures (HeLa). I. The temporal relationships of deoxyribonucleic acid synthesis to mitosis and turnover time. Lab Invest. 1959 Jan-Feb;8(1):278–285. [PubMed] [Google Scholar]
  9. Schaer J. C., Schindler R. The requirement of mammalian cell cultures for serum proteins. Growth-promoting activity of pepsin-digested serum albumin in different media. Biochim Biophys Acta. 1967 Sep 19;147(1):154–161. doi: 10.1016/0005-2795(67)90098-0. [DOI] [PubMed] [Google Scholar]
  10. Schindler R., Hürni C. Synchrony of long duration in suspension cultures of mammalian cells. Nat New Biol. 1971 Dec 1;234(48):148–149. doi: 10.1038/newbio234148b0. [DOI] [PubMed] [Google Scholar]
  11. Schindler R., Ramseier L., Schaer J. C., Grieder A. Studies on the division cycle of mammalian cells. 3. Preparation of synchronously dividing cell populations by isotonic sucrose gradient centrifugation. Exp Cell Res. 1970 Jan;59(1):90–96. doi: 10.1016/0014-4827(70)90627-0. [DOI] [PubMed] [Google Scholar]
  12. Steel G. G. The cell cycle in tumours: an examination of data gained by the technique of labelled mitoses. Cell Tissue Kinet. 1972 Jan;5(1):87–100. doi: 10.1111/j.1365-2184.1972.tb00358.x. [DOI] [PubMed] [Google Scholar]
  13. Tobey R. A., Anderson E. C., Petersen D. F. The effect of thymidine on the duration of G1 in Chinese hamster cells. J Cell Biol. 1967 Oct;35(1):53–59. doi: 10.1083/jcb.35.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES