CIRCADIAN CELL-CYCLE VARIATIONS OF ERYTHROPOIESIS AND MYELOPOIESIS INHUMANS

By use of a multiparameter flow cytometric method with specific surfac e markers, circadian (24-h) variations in cell cycle distribution have been studied in 19 healthy male volunteers by sampling bone marrow (B M) every 4-5 h during 24-h periods. Admixture of peripheral blood duri ng the sampling was specifically adjusted for, and the fractions of ce lls in DNA synthetic phase were measured for different hemopoietic cel l lineages. Significant circadian variations in DNA S-phase were demon strated both in myelo- and erythropoiesis of the human BM, with 75% (m yeloid) and 80% (erythroid) of the volunteers showing highest activity (values) of DNA S-phase during the day and lowest activity (values) b etween midnight and 04:00 h. A temporal relationship in the circadian variation of S-phase and G2/M-phase was demonstrated between the myelo id and erythroid cell lineages. The highest fractions of S-phase cells were found in erythropoiesis, while the highest circadian stage depen dent variation was found in myelopoiesis, The existence of a similar p hasing in DNA synthetic activity for myelopoietic and erythropoietic c ells in the human bone marrow indicates that the circadian rhythmicity of hemopoiesis may be caused by a common regulatory mechanism. These findings may be relevant with regard to optimizing the use of cytotoxi c drugs and hemopoietic growth factors by taking into consideration th e intrinsic (endogenous) circadian variation in proliferative activity of human BM subpopulations.