Blood Journal
Leading the way in experimental and clinical research in hematology

The Effect of Differing Demands for Blood Cell Production on DNA Synthesis by Hemopoietic Colony-Forming Cells of Mice

  1. A. J. BECKER, M.D., Fellow of the Medical Research Council of Canada,
  2. E. A. MCCULLOCH, M.D., F.R.C.P. (C),
  3. L. SIMINOVITCH, PH.D., Professor, and
  4. J. E. TILL, PH.D., Associate Professor
  1. Department of Medical Biophysics, University of Toronto, and The Ontario Cancer Institute, Toronto, Ontario, Canada.
  2. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  3. Associate Professor, Department of Medical Biophysics, University of Toronto.
  4. Associate, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

Abstract

A technic capable of estimating the fraction of hemopoietic colony-forming progenitor cells in DNA synthesis in vivo has been described. The technic is based on the ability of tritiated thymidine to inhibit the growth of those colony-forming cells which, by virtue of their presence in the S-phase during a 20-minute incubation in vitro, in the presence of 500 µc./ml. of H3TdR, have incorporated large amounts of the nucleoside. The method has been applied to transplanted colony-forming cells proliferating in spleens of heavily irradiated recipients as well as to cells from normal fetal liver, normal marrow, and normal spleen. In situations where the hemopoietic system is expanding (fetal liver and regenerating transplants), a large fraction, 40-65 per cent, of the stem cells are in DNA synthesis. In the steady-state situations (adult marrow and spleen), the fraction of cells in DNA synthesis is almost imperceptible using this technic. It is concluded that control mechanisms which govern the rate of hemopoiesis operate, at least in part, by altering the generative cycle of blood-forming progenitor cells.

  • Submitted October 13, 1964.
  • Accepted January 25, 1965.