DNA synthesis in human bone marrow is circadian stage dependent

Abstract

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.