Activity of doxorubicin linked to poly-L-aspartic acid on normal murine hematopoietic progenitor cells.
Compared with free doxorubicin, doxorubicin linked to poly-L-aspartic acid shows a reduction in overall toxicity, without loss of its antitumor activity. In this study, the toxicity of the new anthracycline conjugate on hematopoietic precursor cells of normal DBA/2NCrlBR mice was investigated by assays of bone marrow and spleen CFUs and CFUc (colony-forming units in spleen and culture). In vivo dose- and time-survival curves were determined. Results showed that the conjugate is three to ten times less hematotoxic than doxorubicin. Differences in susceptibility between bone marrow and spleen hematopoietic precursor cells to doxorubicin or the conjugate were observed, suggesting further studies on the pharmacokinetics of the new conjugate.
D000818:Animals; D001772:Blood Cell Count; D001854:Bone Marrow Cells; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000633:toxicity*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010455:Peptides / Q000633:toxicity*; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D010455:Peptides; C050389:doxorubicin polyaspartic acid conjugate; D004317:Doxorubicin