International Journal of Cell Cloning, Vol 10, 87-93, Copyright © 1992 by AlphaMed Press
Comparison of the in vitro toxicity of 2',3'-dideoxynucleosides to murine hematopoietic progenitor cells
DL Du, DA Volpe, CK Grieshaber and MJ Murphy Jr
Hipple Cancer Research Center, Dayton, OH 45439-2092.
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.
