Studies of hematopoietic stem cells spared by 5-fluorouracil
Mouse marrow cells were exposed to 5-fluorouracil (FU) either in vivo or in vitro and the effects on the hematopoietic stem cell compartment were studied. The drug was highly toxic to bone marrow cells including the spleen colony-forming unit (CFU-S) population. The small population of stem cells surviving FU, however, caused a different pattern of spleen colony growth when injected into lethally irradiated mice. Whereas numbers of spleen colonies caused by normal marrow cells remained constant during an 8-14 d period after transplantation, spleen colonies derived from FU-treated marrow cells increased by as much as 100-fold during this time. This effect on stem cells was dose dependent both in vitro and in vivo. When FU was given in vivo, the day 14/day 8 ratio of colonies was greatest 1 d after injection and, over the next 7 d, returned to a near-normal value, that is, unity. A number of studies have shown that the stem cell compartment is heterogeneous with respect to self-replicative capacity and developmental potential. An age structure for the stem cell compartment has been proposed wherein cells with a short mitotic history are more likely to self-replicate than they are to differentiate; hence they are more primitive. I propose that the delayed spleen colony appearance in normal hosts is the result of developmental maturation of the primitive stem cell compartment that survives FU and is responsible for spleen colonies arising around day 14. This maturation, at least initially, occurs in the marrow and leads to the replenishment of the more differentiated CFU-S subsets ablated by FU, which are normally responsible for spleen colonies appearing earlier after transplantation.
- Research Organization:
- Division of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri
- OSTI ID:
- 7133180
- Journal Information:
- J. Exp. Med.; (United States), Vol. 159:3
- Country of Publication:
- United States
- Language:
- English
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FLUOROURACILS
TOXICITY
BONE MARROW CELLS
CFU
IN VITRO
IN VIVO
LETHAL IRRADIATION
MICE
STEM CELLS
SURVIVAL TIME
ANIMAL CELLS
ANIMALS
ANTIMETABOLITES
AZINES
CONNECTIVE TISSUE CELLS
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IRRADIATION
MAMMALS
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIMIDINES
RODENTS
SOMATIC CELLS
URACILS
VERTEBRATES
560152* - Radiation Effects on Animals- Animals
560301 - Chemicals Metabolism & Toxicology- Cells- (-1987)