Toxicity of doxorubicin metabolites to human marrow erythroid and myeloid progenitors in vitro.
Doxorubicin and five synthesized metabolites (doxorubicinol, doxorubicin aglycone, doxorubicinol aglycone, 7-deoxydoxorubicin aglycone, and 7-deoxydoxorubicinol aglycone) were evaluated in vitro for their cytotoxic effect on human marrow erythroid burst- and granulocytic-monocytic colony-forming units (BFU-E, CFU-GM). The IC50 for doxorubicin was 0.39 +/- 0.099 micron and for doxorubicinol was 4.6 +/- 0.63 micron. There was no difference in cytotoxicity for BFU-E or CFU-GM. Incubation with aglycones in concentrations as high as 5.8 micron and prolongation of incubation time for as long as 3 hours had no effect on the growth of BFU-E and CFU-GM in vitro. We conclude that aglycones are not toxic to human marrow erythroid and myeloid progenitors in vitro and do not have a role in the development of doxorubicin-induced myelotoxicity. The mechanism of the lack of cytotoxicity remains unclear.
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Dessypris
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Brenner
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Hande
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects; D006098:Granulocytes / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D009000:Monocytes / Q000187:drug effects
D004317:Doxorubicin; C010013:adriamycinol