Comparison of the in vitro toxicity of 2',3'-dideoxynucleosides to murine hematopoietic progenitor cells.

Abstract

Four nucleoside analogues, 2',3'-dideoxyinosine (ddI), 2',3'-dideoxyadenosine (ddA), 2',3'-dideoxycytosine (ddC) and 5-fluoro-2',3'-dideoxycytosine (5-F-ddC), were evaluated for their potential in vitro myelotoxic effects on normal murine hematopoietic progenitor cells. Myeloid granulocyte-macrophage colony-forming units (CFU-gm), erythroid burst-forming units (BFU-e) and colony-forming units (CFU-e) and megakaryocytic (CFU-meg) progenitors were exposed to the agents for 1 h prior to culture in Petri dish assays or continuously throughout the entire culture period. At 10 microM, both ddA and ddI were moderately toxic (2-36% colony inhibition) to murine CFU-gm, BFU-e, CFU-e and CFU-meg following either 1 h or continuous exposure. Colony inhibition for the progenitors ranged from 2-31% at 10 microM for 1 h ddC or 5-F-ddC exposure. Continuous exposure to ddC was highly myelotoxic to murine hematopoietic progenitors with 100 microM suppressing colony formation 82-89%. At the same concentration and exposure time, 5-F-ddC inhibited colony formation 56-67%. Our results demonstrate that 1 h and continuous exposures to ddA and ddI were similarly myelotoxic to murine hematopoietic cells regardless of exposure time. In contrast, continuous ddC or 5-F-ddC exposure was more toxic to murine progenitors than 1 h exposure to these agents.