Comparison of cytotoxicity of the (−)- and (+)- enantiomer of 2′,3′- dideoxy-3′-thiacytidine in normal human bone marrow progenitor cells

Abstract

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 μM 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 μM, 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).