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Influence of different radioprotective compounds on radiotolerance and cell cycle distribution of human progenitor cells of granulocytopoiesis in vitro
Author(s) -
Klingler Werner,
Kreja Ludwika,
Nothdurft Wilhelm,
Selig Christoph
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03795.x
Subject(s) - cd34 , in vitro , haematopoiesis , peripheral blood mononuclear cell , andrology , microbiology and biotechnology , chemistry , progenitor cell , bone marrow , ficoll , cell culture , pharmacology , cell cycle , apoptosis , stem cell , immunology , medicine , biology , biochemistry , genetics
Summary. Ficoll‐separated mononuclear cells (MNC) of cryopreserved human bone marrow were incubated with isotoxic doses of diltiazem, N‐acetylcysteine (NAC), glycopolysaccharide extract of spirulina platensis (SPE), tempol, thiopental, WR2721 and WR1065. After irradiation with a single dose of 0·73 Gy, survival of granulocyte/macrophage colony‐forming cells (GM‐CFC) was determined at d 10–14, using an agar culture system. Diltiazem, NAC, tempol and WR1065 significantly improved radiotolerance with protection factors (PF) between 1·21 and 1·36 ( n = 5, P < 0·05) at 0·73 Gy (PF‐0·73 Gy). The survival curves of diltiazem (D0 = 0·88 Gy, n = 1·00), NAC (D0 = 0·92 Gy, n = 1·10), tempol (D0 = 0·99 Gy, n = 1·10), WR1065 (D0 = 0·89 Gy, n = 1·16) and control (D0 = 0·78 Gy, n = 1·00) over 0·36–2·91 Gy showed a significant radioprotective effect for D0 only for tempol ( P = 0·018) and for the extrapolation number ‘n’ only in the case of NAC ( P = 0·023). Cell cycle analysis of the CD34 + cell subpopulation (control‐0 h: G1 = 82·7%, S = 13·7%, G2/M = 3·6%) revealed that all compounds with a significant PF‐0·73 Gy also caused a significant increase in CD34 + cells in S phase up to 48 h. Within the first 24 h, only NAC (26·7 ± 4·1%), tempol (14·3 ± 1·0%) and possibly WR1065 (15·5 ± 1·6%) had higher fractions of CD34 + S‐phase cells compared with controls. This observation and the improvement of GM‐CFC cloning efficiency indicated that only NAC was able to recruit progenitor cells in the cell cycle, whereas tempol and WR1065 possibly inhibited cell cycle progression by S and G2/M arrest. Of the radioprotectors tested, NAC, tempol and WR1065 may be suitable to support, alone or combined with cytokine therapy, accelerated haematopoietic recovery after irradiation.