DEFEROXAMINE - A REVERSIBLE S-PHASE INHIBITOR OF HUMAN-LYMPHOCYTE PROLIFERATION

  • 1 January 1984
    • journal article
    • research article
    • Vol. 64  (3) , 748-753
Abstract
Deferoxamine is widely used therapeutically as a chelator of ferric ion in disorders of Fe overload. 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 Fe 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.