Amifostine cytotoxicity and induction of apoptosis in a human myelodysplastic cell line.
Amifostine (AMF), a phosphorylated aminothiol, has been used to treat myelodysplastic syndrome (MDS), where it produces a stimulatory effect on hematopoiesis in bone marrow. To determine if AMF also produced a direct effect on human MDS cells, we planned a study to evaluate the effect of a continuous exposure to AMF on a human MDS cell line. AMF was shown to have a growth-inhibitory effect on MDS cells, with an IC(50) of 14 microM after a 5 day exposure. Cell cycle analysis revealed that a 5 day exposure to 20 microM AMF increased the percentage of cells in G0/G1 and this was accompanied by a decrease in the percentage of cells in S phase. Cytoflorometric and agarose-gel electrophoretic analysis revealed that this effect correlated with cell membrane alterations and DNA fragmentation consistent with an induction of apoptosis without affecting the expression of p53 protein or inducing any lymphoid or myeloid differentiation in the MDS cell line. We conclude that the continuous exposure of a human MDS cell line to AMF is cytotoxic and associated with an induction of apoptosis independent of alterations in p53 expression.
Ribizzi
I
I
Department of Medicine, Rhode Island Hospital and Brown University, Rm 700, 593 Eddy Street, Aldrich Building, Providence, RI 02903, USA.
Darnowski
J W
JW
Goulette
F A
FA
Sertoli
M R
MR
Calabresi
P
P
D004999:Amifostine / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D011837:Radiation-Protective Agents / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D011837:Radiation-Protective Agents; D004999:Amifostine