EFFECT OF DESFERRIOXAMINE AND HYDROXYPYRIDONES ON HEMATOPOIETIC PROGENITORS AND NEUROECTODERMAL TUMOR-CELLS

The iron chelator desferrioxamine (DFO) has been shown to inhibit the proliferation of hemopoietic progenitors and several tumor cell lines. We have compared the in viro hemopoietic inhibitory effect of desferr ioxamine (DFO) and hydroxypyridones (HPOs) on hemopoietic progenitors and two human neuroectodermal (NE) tumor cell lines, NB 100 and SKNMC. Both DFO and HPOs showed a direct dose-related inhibitory effect on B FU-E and CFU-GM obtained from purified human non-T MNAC (T-lymphocyte- depleted nonadherent mononuclear cells) and CD34+ cells. DFO and HPOs displayed both an inhibitory and a cytotoxic effect on NE cell lines. We calculated the ratio between NE cell and hemopoietic cell growth in hibition for a range of concentrations of chelators. DFO showed the mo st satisfactory ratio. This suggests that DFO is still the most prefer able chelating agent for the treatment of neuroblastoma, since it comb ines the highest antineuroblastoma effect with the lowest hematopoieti c toxicity. (C) 1994 Wiley-Liss, Inc.