On control of the hematopoietic cell proliferation.
Hematopoietic cells, detected as spleen colony forming units (CFU-S), vary in their proliferation rate, and this can be investigated in vivo by determining the fraction of CFU-S synthesizing DNA. A large number of measurements of CFU-S number and the fraction synthesizing DNA has been obtained under standardized conditions in normal mice and after a single dose of arabinosyl cytosine (ara-C). These data are analyzed with respect to the correlation between the number of CFU-S and their DNA-synthesizing fraction since, in the past, it has been maintained that the CFU-S proliferation rate responds sensitively to changes in CFU-S numbers. The present analysis does not support this traditional view--it instead demonstrates that natural variations in CFU-S numbers occurring in the same range as those following ara-C do not trigger CFU-S proliferation. On the other hand, administration of ara-C triggers most of the surviving CFU-S into the cell cycle, while decreasing CFU-S numbers by only about 40%. Data are also presented showing changes of CFU-S numbers and their DNA-synthesizing fraction in mice given a single dose of cyclophosphamide (CY). CY reduces CFU-S numbers, but the fraction synthesizing DNA can be either increased or decreased depending on time after treatment. Both these experimental situations argue against a close relationship between CFU-S numbers and their proliferation rate and suggest a different or a more complex regulation.
Necas
E
E
Department of Pathophysiology, First Medical Faculty, Charles University, Prague, Czech Republic.
Sefc
L
L
Znojil
V
V
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013154:Spleen / Q000166:cytology
D003561:Cytarabine; D003520:Cyclophosphamide