5-Fluorouracil effect on cultured murine stem cell progeny and peripheral leukocytes

Pretreatment of mice with 5-fluorouracil (5-FU) depletes total marrow cellularity but leaves a residual population of cells with enhanced regenerative capability. Using the long-term Dexter liquid culture system, we studied the effects of 5-FU on murine marrow cells and their production of pluripotent stem cells (CFU-S) and monocyte-granulocyte precursors (CFU-C). We also examined oxidative and bactericidal activity of neutrophil progeny of marrow cells in culture to determine the effect of 5-FU on effector cell activity. As an in vivo comparison, effector cell activity of neutrophils from peritoneal exudates of 5-FU treated animals was examined. C57B1/6J mice were treated with 5-FU, 100 mg/kg or 150 mg/kg, 4-7 days prior to marrow cell harvest and culture. Total cell counts, CFU-S, and CFU-C were all reduced compared with values from saline-treated controls. Over time, cell production from 5-FU marrow increased, reaching supranormal levels by 2-3 weeks of culture. The neutrophil progeny obtained from these marrow cultures showed normal reduction of nitroblue tetrazolium dye (NBT), but abnormally low chemiluminescence. In contrast, neutrophils from peritoneal exudate of 5-FU-treated animals showed normal chemiluminescence, but abnormally low reduction of NBT. Normal bactericidal activity was exhibited by both neutrophil progeny from marrow cultures and by neutrophils from peritoneal exudates of 5-FU-treated animals. The present data indicate that mouse marrow cells surviving 5-FU have an enhanced proliferative capacity in vitro and are capable of producing neutrophil progeny that, despite some abnormalities of oxidative function, have normal bactericidal capability.