Colony-forming unit-granulocyte-macrophage and DNA synthesis of human bone marrow are circadian stage-dependent and show covariation.

Bone marrow samples from sternum and iliac crests were harvested every 4 hours during 19 24-hour periods from 16 healthy male volunteers, and myeloid progenitor cells were cultured by the colony-forming unit-granulocyte-macrophage (CFU-GM) assay. A large interindividual variation was observed in the mean number of colonies during each 24-hour period, with the highest 24-hour mean colony number being about 600% greater than the lowest (range: 16 +/- 2.3 to 100.3 +/- 4.5). For each individual the difference between the lowest and highest colony number throughout the day ranged from 47.4% to 256.3% of the mean colony number of each series. A circadian stage-dependent variation in the number of colony-forming units of myeloid progenitor cells (CFU-GM) of human bone marrow was demonstrated, with values 150% higher, on the average, during the day as compared with the night. The overall data (891 CFU-GM replicates) exhibited a significant 24-hour rhythm (P less than .001) with an acrophase at midday (12.09 hours with 95% confidence limits from 10.32 to 13.49 hours) and a trough at midnight. This 24-hour variation was found to covary with DNA synthesis in the total proliferating bone marrow cell population. A seasonal effect on CFU-GM numbers was detected by ANOVA (P = .014) and by the least squares fit of a 1-year cosine (P = .015), with the highest number found in summer. The potential relevance of these findings should be examined in relation to cytotoxic cancer therapy, use of hematopoietic growth factors, and bone marrow transplantation.

[1]  Richard J. Jones Autologous bone marrow transplantation , 1993, Current opinion in oncology.

[2]  O D Laerum,et al.  DNA synthesis in human bone marrow is circadian stage dependent. , 1991, Blood.

[3]  R Simon,et al.  Selecting drug combinations based on total equivalent dose (dose intensity) , 1990, Journal of the National Cancer Institute.

[4]  D. Kerr,et al.  The myelotoxicity of carboplatin is influenced by the time of its administration , 1990, Hematological oncology.

[5]  R. Wittes,et al.  Autologous bone marrow transplantation. Current status and future directions. , 1989, Annals of internal medicine.

[6]  Recombinant GM-CSF in myelosuppression of chemotherapy. , 1989, The New England journal of medicine.

[7]  P. Ludman,et al.  DOES STRESSFUL VENEPUNCTURE EXPLAIN INCREASED MIDNIGHT SERUM CORTISOL CONCENTRATION? , 1988, The Lancet.

[8]  A. Reinberg,et al.  Circadian time dependence of murine tolerance for carboplatin. , 1988, Toxicology and applied pharmacology.

[9]  A. Nienhuis Hematopoietic growth factors: biologic complexity and clinical promise. , 1988, The New England journal of medicine.

[10]  W. Hryniuk,et al.  Applications of dose intensity to problems in chemotherapy of breast and colorectal cancer. , 1987, Seminars in oncology.

[11]  R. Klevecz,et al.  Circadian gating of S phase in human ovarian cancer. , 1987, Cancer research.

[12]  V. Devita Dose-response is alive and well. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  W. Hrushesky Circadian timing of cancer chemotherapy. , 1985, Science.

[14]  W. Hryniuk,et al.  The importance of dose intensity in chemotherapy of metastatic breast cancer. , 1984, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  F. Lévi,et al.  Reduction of cis-diamminedichloroplatinum nephrotoxicity in rats by optimal circadian drug timing. , 1982, Cancer research.

[16]  Priv.-Doz. Dr. Hans-Peter Lohrmann,et al.  Recent Results in Cancer Research , 2011 .

[17]  E. Frei,et al.  Dose: a critical factor in cancer chemotherapy. , 1980, The American journal of medicine.

[18]  G. Spitzer,et al.  Diurnal changes in circulating myeloid progenitor cells in man , 1980, American journal of hematology.

[19]  S. Akman,et al.  Diurnal variation of circulating human myeloid progenitor cells. , 1980, Experimental hematology.

[20]  B. Barlogie,et al.  Flow cytometry of DNA content in human bone marrow: a critical reappraisal. , 1980, Blood.

[21]  T. Schlunk,et al.  The influence of culture conditions on the production of colony-stimulating activity by human placenta. , 1980, Experimental Hematology.

[22]  F Halberg,et al.  Methods for cosinor-rhythmometry. , 1979, Chronobiologia.

[23]  A. Burgess,et al.  Stimulation by human placental conditioned medium of hemopoietic colony formation by human marrow cells. , 1977, Blood.

[24]  F. Halberg,et al.  Close reproduction by different laboratories of characteristics of circadian rhythm in 1-beta-D-arabinofuranosylcytosine tolerance by mice. , 1976, Cancer research.

[25]  F. Halberg,et al.  Increased Tolerance of Leukemic Mice to Arabinosyl Cytosine with Schedule Adjusted to Circadian System , 1972, Science.

[26]  A. Mauer,et al.  DIURNAL VARIATION OF PROLIFERATIVE ACTIVITY IN THE HUMAN BONE MARROW. , 1965, Blood.

[27]  E. Cronkite,et al.  Mitotic indices of human bone marrow cells. I. Number and cytologic distribution of mitoses. , 1962, Blood.

[28]  D. Buttenberg,et al.  [Chemotherapy of advanced ovarian cancer]. , 1960, Die Medizinische Welt.