Adherent-cell-dependent stimulation of CFU-GM by nucleobases, nucleosides, their analogues, and the hemoregulatory peptide dimer.
At suboptimal concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), nucleobases and nucleosides as well as their analogues strongly stimulated aggregate (colony and cluster) formation from murine bone marrow granulocyte-macrophage colony-forming units (CFU-GM) in agar culture. Active compounds include 2'-deoxycytidine, thymidine, 5'-deoxyarabinosyl-cytosine, 5'-deoxy-5'-fluorothymidine, uracil, 6-methyluracil, orotic acid, and also purine derivatives as adenine, guanine, adenosine, and guanosine. The stimulation was almost identical to that obtained with the dimer of the hemoregulatory pentapeptide. In the absence of colony-stimulating factor (CSF) no stimulation was seen. After separation of adherent cells from the bone marrow cells, the stimulatory effect was lost. It also decreased when the number of bone marrow cells plated was diminished. This suggests that the tested compounds induce growth factor production in adherent cells. The structure/activity relationships indicate that the active compounds are nucleosides, or they may serve for nucleoside synthesis inside the cell. However, nucleotide formation is not necessary for activity.
Langen
P
P
Central Institute of Molecular Biology, Berlin-Buch, Germany.
Schunck
H
H
Hunger
B
B
Schütt
M
M
Laerum
O D
OD
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D003841:Deoxycytidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008811:Mice, Inbred DBA; D009705:Nucleosides / Q000494:pharmacology*; D009711:Nucleotides / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives
D003115:Colony-Stimulating Factors; D006131:Growth Inhibitors; D009705:Nucleosides; D009711:Nucleotides; D009842:Oligopeptides; D003841:Deoxycytidine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C040758:hemoregulatory peptide 5b; D011761:Pyrrolidonecarboxylic Acid