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Deferoxamine: a reversible S-phase inhibitor of human lymphocyte
proliferation
HM Lederman, A Cohen, JW Lee, MH Freedman and EW Gelfand
Deferoxamine is widely used therapeutically as a chelator of ferric ion in
disorders of iron overload. This study demonstrates that this drug is a
potent inhibitor of DNA synthesis by human B and T lymphocytes in vitro,
but has relatively little effect on the synthesis of RNA and protein. The
inhibitory effects of deferoxamine are completely reversible by washing or
by adding stoichiometric amounts of Fe3+. Micromolar concentrations of
deferoxamine decrease intracellular levels of deoxyribonucleoside
triphosphates, which is similar to the effects of hydroxyurea. The binding
of iron by deferoxamine likely causes an inhibition of ribonucleotide
reductase activity, thereby preventing cells from completing the S phase of
the cell proliferation cycle. As a reversible and nontoxic S-phase
inhibitor, it may have important experimental and therapeutic applications.
Volume 64,
Issue 3,
pp. 748-753,
09/01/1984
Copyright © 1984 by The American Society of Hematology
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