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DNA synthesis in human bone marrow is circadian stage dependent
R Smaaland, OD Laerum, K Lote, O Sletvold, RB Sothern and R Bjerknes
Gade Institute, Department of Pathology, Haukeland Hospital, University of
Bergen, Norway.
Fraction of human bone marrow (BM) cells in DNA synthesis has been studied
by sampling BM from the sternum or the iliac crests every 4 hours during
one 24-hour period in 16 healthy male volunteers. Three of the subjects
underwent the sampling procedure twice, resulting in 19 24- hour profiles.
The percentage of cells in DNA synthesis measured by flow cytometry
demonstrated a large variation along the circadian time scale for each
24-hour profile, with a range of variation from 29% to 339% from lowest to
highest value. Seventeen profiles (89.5%) had the highest DNA synthesis
during waking hours between 08:00 hours and 20:00 hours, and the lowest
percentage of cells in DNA synthesis between 00:00 hours and 04:00 hours.
The mean value of the lowest DNA synthesis for each 19 24-hour period was
8.7% +/- 0.6%, while the mean value of the highest DNA synthesis was 17.6%
+/- 0.6%, ie, a twofold difference. There was no difference in DNA
synthesis between winter and summer. A significantly higher DNA synthesis
was demonstrated for samples obtained from sternum as compared with the
iliac crests, but the same circadian pattern was demonstrated for both
localizations. By taking circadian stage-dependent variations in DNA
synthesis into account it may be possible to reduce BM sensitivity to
cytotoxic chemotherapy, to increase the effect of hematopoietic growth
factors as well as increase the fraction of proliferating cells with
careful selection of time of day for harvesting BM cells for auto- or
allografting.
Volume 77,
Issue 12,
pp. 2603-2611,
06/15/1991
Copyright © 1991 by The American Society of Hematology
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