Characterization of megakaryocyte spleen colony-forming units by response to 5-fluorouracil and by unit gravity sedimentation

Journal Article · Sat Oct 01 04:00:00 EDT 1983 · Blood; (United States)

OSTI ID:5427746

Thean, L E; Hodgson, G S; Bertoncello, I; Radley, J M

Properties of megakaryocyte progenitor cells in mouse bone marrow have been examined using an in vivo assay system. Perturbation with 5-fluorouracil (5-FU) and separation by unit gravity sedimentation was used to characterize the cells. Bone marrow was assayed for the presence of megakaryocyte colony-forming cells (MK CFU-S) by transplantation into lethally irradiated mice and examining spleen sections 10 days later. Donor mice were untreated or injected intravenously with 5-FU (150 mg/kg), 1 (FU-1) or 7 (FU-7) days beforehand. There was a lack of correlation between the numbers of MK CFU-S and cells giving rise to macroscopic spleen surface colonies (CFU-S10). The sedimentation profile of MK CFU-S in normal marrow was similar (modal velocity 4.16 +/- 0.05 mm/hr) to that of CFU-S10. In FU-1 marrow, MK CFU-S exhibited a bimodal sedimentation profile, with peaks at 3.26 +/- 0.06 mm/hr and 4.53 +/- 0.07 mm/hr. The marrow content of CFU-S10 was reduced to 5% of normal, while MK CFU-S numbers were only reduced to 60%. In FU-7 marrow, the sedimentation profile of MK CFU-S (modal velocity 4.86 +/- 0.16 mm/hr) differed from that of CFU-S10 (5.5 +/- 0.16 mm/hr). It was concluded MK CFU-S and CFU-S10 are different entities. The MK colonies formed from FU-1 marrow contained on average 3.8-fold more cells than those formed from normal marrow. The enhanced megakaryocyte production may be accounted for on the basis of the generation-age model for cell proliferation. It is proposed that MK CFU-S are a heterogeneous population with regard to proliferation potential and that the FU-1 marrow contains cells that survive 5-FU and have a high proliferative potential. These cells may be equivalent among megakaryocytic progenitors to the high proliferative potential colony-forming cells of the granulocyte/macrophage series. They may be responsible for the enhanced megakaryocytopoiesis seen in the marrow of mice 7 days after the injection of 5-FU.

• Research Organization: Biological Research Unit, Cancer Institute, Melbourne, Victoria, Australia
• OSTI ID: 5427746
• Journal Information: Blood; (United States), Journal Name: Blood; (United States) Vol. 62:4; ISSN BLOOA
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTIMETABOLITES
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
BONE MARROW CELLS
CHIMERAS
COLONY FORMATION
CONNECTIVE TISSUE CELLS
DRUGS
FLUOROURACILS
HEMATOPOIETIC SYSTEM
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IRRADIATION
LETHAL IRRADIATION
MAMMALS
MICE
MOSAICISM
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIMIDINES
RADIATION EFFECTS
RODENTS
SEDIMENTATION
SOMATIC CELLS
SPLEEN
SPLEEN COLONY FORMATION
STEM CELLS
URACILS
VERTEBRATES