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Colony-forming unit-granulocyte-macrophage and DNA synthesis of human bone
marrow are circadian stage-dependent and show covariation
R Smaaland, OD Laerum, RB Sothern, O Sletvold, R Bjerknes and K Lote
Gade Institute, Department of Pathology, Haukeland Hospital, University of
Bergen, Norway.
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.
Volume 79,
Issue 9,
pp. 2281-2287,
05/01/1992
Copyright © 1992 by The American Society of Hematology
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