Drugs elevating extracellular adenosine promote regeneration of haematopoietic progenitor cells in severely myelosuppressed mice: their comparison and joint effects with the granulocyte colony-stimulating factor

: We tested capabilities of drugs elevating extracellular adenosine and of granulocyte colony‐stimulating factor (G‐CSF) given alone or in combination to modulate regeneration from severe myelosuppression resulting from combined exposure of mice to ionizing radiation and carboplatin. Elevation of ex...

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Published in:	European journal of haematology Vol. 68; no. 1; pp. 4 - 11
Main Authors:	Hofer, Michal, Pospı´šil, Milan, Znojil, Vladimı´r, Vacek, Antonı´n, Weiterová, Lenka, Holá, Jiřina, Vácha, Jiřı´
Format:	Journal Article
Language:	English
Published:	Oxford, UK Munksgaard International Publishers 01-01-2002 Blackwell
Subjects:	Adenosine - metabolism adenosine monophosphate Adenosine Monophosphate - pharmacology Adenosine Monophosphate - therapeutic use Animals Biological and medical sciences Blood Cell Count Blood. Blood coagulation. Reticuloendothelial system Bone Marrow - drug effects Bone Marrow - pathology Bone Marrow - radiation effects Carboplatin - toxicity cytostatic drugs dipyridamole Dipyridamole - pharmacology Dipyridamole - therapeutic use Drug Evaluation, Preclinical Drug Synergism Erythroid Precursor Cells - pathology extracellular adenosine Extracellular Space - metabolism G-CSF Granulocyte Colony-Stimulating Factor - pharmacology Granulocyte Colony-Stimulating Factor - therapeutic use Hematopoietic Stem Cells - pathology ionizing radiation Lymphocytes - pathology Macrophages - pathology Male Medical sciences Mice Mice, Inbred C57BL Mice, Inbred CBA myelosuppression Pancytopenia - drug therapy Pancytopenia - etiology Pancytopenia - metabolism Pancytopenia - pathology Pharmacology. Drug treatments Prodrugs - pharmacology Prodrugs - therapeutic use Whole-Body Irradiation - adverse effects Animal model Adenosine AMP Toxicity Stem cell Cytokine Rodentia Dipyridamole Hematopoietic cell Extracellular Vertebrata Chemotherapy Granulocyte colony stimulating factor Immunosuppression Ionizing irradiation Mammalia Treatment Mouse Polypeptide Animal Complication Mechanism of action
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Summary:	: We tested capabilities of drugs elevating extracellular adenosine and of granulocyte colony‐stimulating factor (G‐CSF) given alone or in combination to modulate regeneration from severe myelosuppression resulting from combined exposure of mice to ionizing radiation and carboplatin. Elevation of extracellular adenosine was induced by joint administration of dipyridamole (DP), a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), serving as an adenosine prodrug. DP + AMP, G‐CSF or all these drugs in combination were administered in a 4‐d treatment regimen starting on day 3 after induction of myelosuppression. Comparable enhancements of haematopoietic regeneration due to elevation of extracellular adenosine or to action of G‐CSF were demonstrated as shown by elevated numbers of haematopoietic progenitor cells for granulocytes/macrophages (GM‐CFC) and erythrocytes (BFU‐E) in the bone marrow and spleen in early time intervals after termination of the drug treatment, i.e. on days 7 and 10 after induction of myelosuppression. Coadministration of all the drugs further potentiated the restoration of progenitor cell pools in the haematopoietic organs. The effects of the drug treatments on progenitor cells were reflected in the peripheral blood in later time intervals of days 15 and 20 after induction of myelosuppression, especially as significantly elevated numbers of granulocytes and less pronounced elevation of lymphocytes and erythrocytes. The results substantiate the potential of drugs elevating extracellular adenosine for clinical utilization in myelosuppressive states, e.g. those accompanying oncological radio‐ and chemotherapy.
Bibliography:	istex:F3D314144BD2B3FAE8BE35ACD600CD2B3562ED16 ArticleID:EJH564 ark:/67375/WNG-D2CXKKB4-G
ISSN:	0902-4441 1600-0609
DOI:	10.1034/j.1600-0609.2002.00564.x