The role of polyamine biosynthesis in hematopoietic precursor cell
proliferation in mice
E Niskanen, A Kallio, PP McCann and DG Baker
Under the influence of a selective irreversible inhibitor of ornithine
decarboxylase (ODC), DL-alpha-difluoromethylornithine (DFMO), early
hematopoiesis was enhanced. In the bone marrow, the absolute number of
cells that give rise to spleen colonies in lethally irradiated mice
(CFU-S), granulocytic colonies in diffusion chambers in mice (CFU-DG), and
granulocyte-monocyte colonies in agar in vitro (CFU-C) was increased 2-4
fold. This could be abrogated by administration of putrescine, confirming
the association of the stimulatory effect with polyamine biosynthesis most
likely via depression of ornithine decarboxylase activity and subsequent
synthesis of putrescine. Analysis of cell cycle characteristics by 3H-TdR
suicide technique demonstrated that the proportion of CFU-S, CFU-DG, and
CFU-C in S-phase was significantly increased. Additionally, the stimulatory
effect was reflected by enhanced colony formation in diffusion chambers
implanted intraperitoneally in mice receiving DFMO. This could also be
eliminated by treatment of the host animal with putrescine, again
suggesting that polyamine biosynthesis plays an important role at the early
stages of hematopoiesis in vivo. Effect of DFMO on colony formation in
vitro (CFU- C) was inhibitory and not reversible with putrescine. It could
be partially eliminated by aminoguanidine, which neutralizes diamine
oxidase present in fetal calf serum used in the CFU-C assay. These data
suggest that the effect of DFMO in vitro was nonspecific.
Volume 61,
Issue 4,
pp. 740-745,
04/01/1983
Copyright © 1983 by The American Society of Hematology
