Lithium and hematopoietic toxicity. II. Acceleration in vivo of murine hematopoietic progenitor cells (CFU-gm and CFU-meg) following treatment with vinblastine sulfate.
Suppression of hematopoiesis is far too often the main consequence of antineoplastic therapy, such that the developing degree of myelosuppression and/or thrombocytopenia are usually the rate-limiting steps to adjuvant therapy. This communication reports the results of studies designed to investigate the capability of lithium to accelerate in vivo hematopoietic recovery following exposure to vinblastine sulfate (VB). Male mice (144 BC3F1) received VB (4 mg/kg/b.w.) i.v. Twenty-four h following VB, 72 mice received 35 micrograms m/animal, ultra-pure lithium carbonate (Li2CO3) i.p. Another 72 mice received either VB or phosphate buffered saline as controls. Beginning 24 h later and continuing on days 2, 5, 7, 9, 12, 21 and 28, three mice from each group were randomly sacrificed and their hematological parameters analyzed. Bone marrow and splenic granulocyte-macrophage progenitor cells (CFU-gm) and megakaryocyte progenitor cells (CFU-meg) content were evaluated. Lithium was unable to prevent the onset of either neutropenia or thrombocytopenia; however, lithium was successful in restoring normal white blood cell and platelet values earlier than the VB control group, thus significantly reducing the period of drug-induced neutropenia and thrombocytopenia. This lithium-enhanced hematopoiesis was measured by an accelerated recovery in both marrow and splenic CFU-gm and CFU-meg compared to controls. These data demonstrate the efficacy of lithium to accelerate hematopoietic recovery following exposure to cytotoxic antineoplastic drugs.
D000818:Animals; D001854:Bone Marrow Cells; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D007958:Leukocyte Count / Q000187:drug effects; D008094:Lithium / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D010976:Platelet Count / Q000187:drug effects; D013154:Spleen / Q000166:cytology; D014747:Vinblastine / Q000037:antagonists & inhibitors*
D014747:Vinblastine; D008094:Lithium