Altered sensitivity of hematopoietic stem cells to 5-fluorouracil (NSC-19893) following endotoxin (NSC-189681), cyclophosphamide (NSC-26271), or irradiation

Hematopoietic cells that form colonies in the spleen (CFU-S) or in culture (CFU-C) from the marrow of endotoxin-treated mice become markedly sensitive to a 6-hour in vivo exposure to 2.5 mg of 5-fluorouracil (5-FU). It was therefore suggested that short exposures to 5-FU (2.5 mg given 6 hours before the animals were killed) could be used to follow changes in the sensitivity of CFU-S and CFU-C after several treatments which might stimulate the proliferation of marrow colony-forming cells. After 25 μ g of endotoxin was given, a maximum reduction (approximately 100-fold) in the number of colony-forming cells in 5-FU-treated mice occurred at 36 hours, with recovery to starting values by 72 hours. Similar changes in sensitivity to 5-FU were also seen in mice whose marrows were undergoing hematopoietic regeneration after 3 mg of cyclophosphamide or 150 rads of total-body irradiation. These results indicate that agents which perturb the marrow may be quantitatively examined on the basis of their ability to alter the sensitivity of hematopoietic progenitor cells to chemotherapeutic agents. (U.S.)