Hematopoietic precursor cells in mice treated with 4-demethoxydaunorubicin and doxorubicin.
The hematologic toxicity of 4-demethoxydaunorubicin (4-dmDNR), a new anthracycline more potent and less cardiotoxic than doxorubicin (Dx), was studied. Dose-survival curves of bone marrow hematopoietic precursor cells (HPC) in situ were determined with the use of (C57BL X C3H)F1 mice and with assays of colony-forming units--spleen, culture, and erythroid--by in vivo and in vitro methods. Time response of HPC was followed in mice treated at days 0, 2, and 5 with 0.75 mg 4-dmDNR/kg of 4.5 mg Dx/kg and in mice receiving 2.23 mg 4-dmDNR/kg or 3.96 mg Dx/kg twice a week for 4 weeks. The dose-survival curves of HPC for 4-dmDNR were exponential. Slight differences in sensitivity among assayed populations were seen. Although the doses of 4-dmDNR required to reduce the survival of HPC to 37% were similar or lower than those of Dx, following intermittent treatment with doses of 4-dmDNR with the same optimal antitumor activity as with Dx, 4-dmDNR seemed to have a lesser effect on hematopoietic progenitors and a greater effect on peripheral blood cells than did Dx. However, during prolonged administration 4-dmDNR appeared to be toxic at every hematopoietic level.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D015255:Idarubicin; D051379:Mice; D008810:Mice, Inbred C57BL; D012156:Reticulocytes / Q000187:drug effects; D013997:Time Factors
D004317:Doxorubicin; D015255:Idarubicin; D003630:Daunorubicin