EFFECTS OF ENDOTOXIN AND EXTRACTS OF PREGNANT MOUSE UTERUS ON THE RECOVERY OF HEMATOPOIESIS AFTER 5-FLUOROURACIL

Abstract

A single injection of endotoxin [Salmonella typhi], 4 h after administration of 150 mg/kg of 5-fluorouracil (5-FU), stimulated the recovery of bone marrow hemopoietic cells that form colonies in spleen (CFU-S) [pluripotential stem cells] or in culture (GM-CFC) [granulocyte-macrophage colony forming cells], of erythropoiesis and of platelet production. Corynebacterium parvum [Propionibacterium acnes] injections had similar effects. Endotoxin-free extracts of tissues (from pregnant mouse uterus, placenta and embryo) which have a high content of the factor(s) (CSF) capable of stimulating growth of GM-CFC in vitro also stimulated recovery of CFU-S and GM-CFC when given in single injections 4 h after 5-FU. A striking effect of endotoxin and tissue extracts was the acceleration of the regeneration of a particular subclass of granulocyte macrophage progenitors, those capable of forming large colonies (> 0.25 mm) in agar. Apparently, recovery of hemopoiesis after depression by 5-FU can be stimulated not only by injection of bacterial products, but also by injection of endotoxin-free tissue extracts which contain high levels of hemopoietic regulators like CSF.