THE TETRAPEPTIDE ACSERASPLYSPRO (SERASPENIDE), A HEMATOPOIETIC INHIBITOR, MAY REDUCE THE IN-VITRO TOXICITY OF 3'-AZIDO-3'-DEOXYTHYMIDINE TOHUMAN HEMATOPOIETIC PROGENITORS

3'-azido-3'-deoxythymidine (AZT), the main antiviral drug used in AIDS treatment, is known to induce anemia and neutropenia. These effects h ave been attributed to its toxicity to hematopoietic progenitors. In t his report, we present a new approach to reduce AZT hematotoxicity by using an inhibitory factor of the hematopoietic stem cells, the tetrap eptide AcSerAspLvsPro (AcSDKP, Seraspenide), which has been shown to i ncrease the survival of mice subjected to high doses of chemotherapy a nd to block reversibly the cycling of human granulocyte-macrophage col ony forming unit (CFU-GM) and burst forming unit erythroid (BFU-E) pro genitors. Normal bone marrow mononuclear cells (BMMNC) from 14 subject s were incubated with or without AcSDKP (10(-10) M) for 20 h and with or without AZT (100 muM) for another 2 h. After washing, cells were pl ated in methylcellulose in the presence of interleukin 3 (IL-3), granu locyte-macrophage colony stimulating factor (GMCSF) and erythropoietin (EPO). Under these conditions, the preincubation of cells with AcSDKP reduced significantly the toxicity of AZT to both BFU-E and CFU-GM at least in 3 out of 8 and 4 out of 10 cases, respectively. A careful st atistical analysis of these observations indicates that AcSDKP may be an efficient factor in preserving progenitors against AZT-induced hema topoietic toxicity.