Effects of 5-fluorouracil on Mouse Bone Marrow

5-Fluorouracil (150 mg/kg) was injected intravenously into 11-week-old male mice. Its effects on marrow structure over the following 9 d were assessed using light microscopic examination of semi-thin transverse sections of decalcified humeri. The extravascular compartment became markedly depleted of cells and decreased in size, reaching a minimum on day 5 post-treatment. Proliferating haematopoietic cells disappeared within 2 d. Post-replicative erythrocytic cells underwent extra-vascular phagocytosis by resident macrophages, whilst mature granulocytes continued to pass into the circulation. Repopulation was underway by day 6, and re-expansion of the extravascular compartment by day 7 when megakaryocytes, of larger than normal average size, occupied most of the extravascular compartment. Megakaryocyte dominance gave way over days 8 and 9 as other haematopoietic cells proliferated and the extravascular compartment continued to enlarge. The significance of the results is discussed in relation to marrow micro-circulation, egress of haematopoietic cells into the circulation, and cell proliferation in the marrow. Endotoxin, administered 4 h after 5-fluorouracil, accelerated depletion of the marrow and recovery of haematopoiesis by about 1 d.