The pattern of myeloid suppression and recovery after the addition of methotrexate to murine long-term bone marrow culture.
Treating long-term bone marrow culture with 10(-7)-10(-5) M methotrexate caused a 95% reduction in myelopoiesis as assessed by supernatant cell count and granulocyte/macrophage colony forming unit number. The suppression was irreversible with 10(-5) M methotrexate. Complete recovery of myeloid cell production occurred four and five weeks after cultures were treated with either 10(-7) M or 10(-6) M methotrexate, respectively. The suppression of myelopoiesis was completely prevented if 10(-3) M leucovorin was added to culture within 6 h of 10(-6) M methotrexate. The addition to culture of lung conditioned medium containing high concentrations of granulocyte/macrophage colony-stimulating factor shortened the time of myelopoietic suppression by one week. The addition of WEHI-3B medium containing both interleukin 3 and GM-CSF shortened the suppression by two weeks. This in vitro model provides unique opportunities to examine mechanisms involved in the myelopoietic and chemotherapy-induced suppression. A close analysis of approaches to modify the recovery process will also be possible.
Udupa
K B
KB
Geriatric Research, Education and Clinical Center (GRECC), John L. McClellan Veterans Administration Hospital, Little Rock, AR.
Lipschitz
D A
DA
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D007700:Kinetics; D002955:Leucovorin / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
D002955:Leucovorin; D008727:Methotrexate