Reduction of Busulfan-Induced Granulocytopoietic Toxicity in Mice by Postbusulfan Injection of Endotoxin 1

Abstract

Abstract

Busulfan produces profound and prolonged hematopoietic depression in mice. However, the decline in pluripotent cell compartments such as those forming spleen colonies (CFU-S) is much more precipitate than the decline in their progeny such as cells forming colonies in methylcellulose (CFU-C) or in granulocytes. Endotoxin was given immediately following a single 60 mg/kg dose of busulfan in order to determine its influence upon the subsequent decline and recovery of CFU-C, total nucleated cells, and marrow granulocytes/humerus. There was no effect on the rate of decline for 3 days following busulfan. However, the decline slowed in endotoxin treated mice on the 4th day and all three values were significantly higher than in controls on Day 5, the nadir for controls. Controls had an abortive recovery evident by Day 7. At this time endotoxin treated mice had higher values than in controls for total nucleated cells and granulocytes, but not for CFU-C. By Day 9, no further effect of endotoxin could be demonstrated. This effect is similar to that of androgenic steroids on the granulocytic system of busulfan-treated mice. The simplest explanation for the effect is to suggest that CFU-C are capable of self-replication and that endotoxin stimulates this self-replication.