Comparison of cytotoxicity of the (-)- and (+)-enantiomer of 2',3'-dideoxy-3'-thiacytidine in normal human bone marrow progenitor cells.
The effects of racemic cis-2',3'-dideoxy-3'-thiacytidine [(+/-)-BCH-189] and its two enantiomers on human myeloid and erythroid colony-forming cells were studied by clonogenic assays. The (+)-isomer was the most toxic with a median inhibitory concentration approximating 2 microM in both cell lineages. In contrast, concentrations of the (-)-isomer required for 50% inhibition of granulocyte macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) were 33.9 +/- 15.1 and 169.4 +/- 87.9 microM, respectively. The racemic BCH-189 was quite toxic to these cells, but to a lesser extent than observed with 3'-azido-3'-deoxythymidine and 3'-fluoro-3'-deoxythymidine (positive controls).
Sommadossi
J P
JP
Department of Pharmacology, University of Alabama, Birmingham, AL 35294.
Schinazi
R F
RF
Chu
C K
CK
Xie
M Y
MY
D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D015224:Dideoxynucleosides / Q000494:pharmacology; D006098:Granulocytes / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D019259:Lamivudine; D008264:Macrophages / Q000187:drug effects; D013237:Stereoisomerism; D016047:Zalcitabine / Q000031:analogs & derivatives* / Q000494:pharmacology
D015224:Dideoxynucleosides; D019259:Lamivudine; D016047:Zalcitabine; C002854:alovudine