Faculty Research 1990 - 1999

Title

Assessing permanent damage to primitive hematopoietic stem cells after chemotherapy using the competitive repopulation assay.

Document Type

Article

Publication Date

1993

Keywords

Antineoplastic-Agents: to, Cell-Division: de, Colony-Forming-Units-Assay, Hematopoietic-Stem-Cells: de, In-Vitro, Male, Mice, Mice-Inbred-C57BL, SUPPORT-U-S-GOVT-P-H-S

JAX Source

Cancer Chemother Pharmacol 1993;32(6):450-4

Grant

DK25687/DK/NIDDK, AG00594/AG/NIA, AG06232/AG/NIA

Abstract

The competitive repopulation assay was used to document the effects of six chemotherapeutic agents on primitive hematopoietic stem cells. The assay measures the relative abilities of donor cells to produce circulating erythrocytes and lymphocytes in lethally irradiated congeneic mice over a period of 6 months. Long-lasting marrow reconstitutive deficits in cells of donor origin occurred after exposure to 5-fluorouracil (5FU), bis-chloronitrosourea (BCNU), cyclophosphamide (CTX), vincristine (VCR), and actinomycin D (ACT) but not after exposure to cytosine arabinoside (ARA). Repopulating abilities were reduced after as little as a single dose of CTX or BCNU. A second dose of BCNU caused even more severe effects. A single dose of 5FU had no effect on repopulating abilities despite a temporary 10-fold reduction in marrow cell number, but multiple doses reduced the marrow stem-cell replicative ability to less than half of the normal control levels. These effects were not reliably predicted or detected by colony-forming assays or by reductions in marrow cell number. Thus, long-lasting proliferative defects in the primitive hematopoietic stem-cell (PHSC) population can result from the use of chemotherapeutic agents. Such findings may have clinical implications, especially in individuals receiving repeated or prolonged administration of these agents or in instances of marrow transplantation.

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