Effects of bleomycin on mouse bone-marrow stem cells.
The mouse hematopoietic stem-cell population was tested by the spleen colony technique for effects of the antineoplastic agent bleomycin (BLM). The time response of normal bone marrow was investigated by a single dose of BLM (400 mg/kg) between 0 and 72 hours. The dose response was studied over a wide range of doses (from 40 to 1,600 mg/kg) at a 4-hour exposure. Additional experiments concerned 1) the fraction of colony-forming units in the S phase after BLM administration (by means of pulse hydroxyurea treatment), 2) the response of bone marrow stimulated by endotoxin, and 3) the effects of split-dose treatments. The relatively low toxicity of BLM on both the differentiated and stem-cell populations of unstimulated bone marrow was confirmed and detailed. This drug exhibited peculiar, proliferation-dependent cell inactivation kinetics. Furthermore, BLM induced parasynchronous behavior in the unstimulated stem-cell population. The various aspects of BLM action are discussed with regard to its use in cancer chemotherapy.
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006918:Hydroxyurea / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000187:drug effects; D013154:Spleen; D013268:Stimulation, Chemical; D013997:Time Factors
D004731:Endotoxins; D001761:Bleomycin; D006918:Hydroxyurea