Lithium and hematopoietic toxicity. I. Recovery in vivo of murine hematopoietic stem cells (CFU-S and CFU-Mix) after single-dose administration of cyclophosphamide.
Studies are described that demonstrate the ability of lithium (Li) to enhance the recovery of the total peripheral blood neutrophil and pluripotential stem cell (CFU-S and CFU-Mix) populations per femur from mice administered cyclophosphamide (CTX)(200 mg/kg body weight). Beginning 2 h after CTX administration and on the following two days, mice received ultra-pure Li2CO3 (35 micrograms/kg body weight) intraperitoneally. Control groups consisted of mice receiving either CTX or phosphate-buffered saline only; 24 h later and, on days 2-5, 7, 9, 12, 14, 16, 21, and 28, three mice from each group were serially sacrificed. Peripheral blood was obtained and examined for their hematocrit, white blood cell (WBC), and differential values. Bone marrow was harvested and assayed in vivo for CFU-S and in vitro for CFU-Mix. In addition, cell-cycle status of regenerating marrow was evaluated in vitro by use of the hydroxyurea suicide technique. Mice receiving CTX plus Li developed a significant elevation in the WBC which was demonstrated by an increase in the total neutrophil population when compared with CTX-administered controls. This enhanced hematopoietic activity was further demonstrated by an accelerated recovery of CFU-S and CFU-Mix compared with CTX controls. Cell kinetic studies demonstrated that a greater percentage of these stem cells obtained from Li-treated animals were in active cell cycle. These results demonstrate and confirm the capability of Li to accelerate hematopoietic recovery following the use of agents known to suppress hematopoiesis.
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D000818:Animals; D003520:Cyclophosphamide / Q000008:administration & dosage*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006918:Hydroxyurea / Q000494:pharmacology; D007958:Leukocyte Count; D008094:Lithium / Q000633:toxicity*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils
D003520:Cyclophosphamide; D008094:Lithium; D006918:Hydroxyurea