ULTRASTRUCTURAL-CHANGES OF STROMAL CELLS OF BONE-MARROW AND LIVER AFTER CYCLOPHOSPHAMIDE TREATMENT IN MICE

The direct effect of cyclophosphamide (CY) on bone marrow and liver st romal cells of DBA/2 and C57BL/6 mice after a single intraperitoneal d ose of 300 mg/kg, was assessed. Ultrastructural observations were carr ied out 2,4,6,12,18, and 24 h and 2,3,5,7,10,15,22 and 30 days after C Y in femoral bone marrow and liver fixed by immersion or vascular perf usion. A massive depletion of hemopoietic cells was observed in bone m arrow as early as 12 h after CY treatment, and normality was recovered only after 10 days. Among stromal cells, sinus endothelial cells, ret icular cells, and macrophages were particularly sensitive to CY and sh owed severe damage as soon as 2 h after treatment. There was also an i mportant dilatation of sinusoids, and the presence of mature red cells in the hemopoietic parenchyma, and macrophages and immature cells in the lumen and in circulating blood demonstrated the loss of integrity of the endothelium. In the liver, injured cells showing vesiculation a nd disruption of endothelial and Kupffer cells of sinusoids were evide nt 6 h after CY. The alterations caused by CY were transient. Although recovery of the hemopoietic cells in bone marrow and liver was achiev ed by day 10, the stromal cells showed damage even 15 days after CY, a nd a return to normality was only reached on day 30. Thus, the effect of CY on stromal cells, that was longer lasting than the effect on the hemopoietic compartment, demonstrated a higher recovery capacity of h emopoiesis with respect to stromal cells. These results demonstrate th at recovery of hemopoiesis occurred even while the severe damage infli cted by CY to the stromal cells remained unrepaired.