Amifostine cytotoxicity and induction of apoptosis in a human myelodysplastic cell line

Amifostine (AMF), a phosphorylated aminothiol, has been used to treat myelo dysplastic syndrome (MDS), where it produces a stimulatory effect on hemato poiesis in bone marrow. To determine if AMF also produced a direct effect o n human MDS cells, we planned a study to evaluate the effect of a continuou s exposure to AMF on a human MDS cell line. AMF was shown to have a growth- inhibitory effect on MDS cells, with an IC50 of 14 mu M after a 5 day expos ure. Cell cycle analysis revealed that a 5 day exposure to 20 mu M AMF incr eased the percentage of cells in G0/G1 and this was accompanied by a decrea se in the percentage of cells in S phase. Cytoflorometric and agarose-gel e lectrophoretic analysis revealed that this effect correlated with cell memb rane alterations and DNA fragmentation consistent with an induction of apop tosis without affecting the expression of p53 protein or inducing any lymph oid or myeloid differentiation in the MDS cell line. We conclude that the c ontinuous exposure of a human MDS cell line to AMF is cytotoxic and associa ted with an induction of apoptosis independent of alterations in p53 expres sion. (C) 2000 Elsevier Science Ltd. All rights reserved.