N-6-Cyclopentyladenosinc haematopoietic inhibits proliferation of murine progenitor cells in vivo
Effects of N-6-cyclopentyladenosine (CPA), the selective adenosine A I receptor agonist, on bone marrow haematopoietic progenitor cells for granulocytes and macrophages (CFC-GM) were investigated by utilizing the model of haematopoietic damage induced by 5-fluorouracil. Experiments were performed in vivo on B10CBAF(1) mice. A single i.p. injection of CPA at the optimum dose of 200 nmol/kg administered 22 h before a single injection of 5-fluorouracil (100 mg/kg, i.p.) protected CFC-GM against the cytotoxic damage as determined 4 days later. Isomolar doses of the selective agonists for adenosine A(2A) receptors, i.e. 2-p-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine, and for adenosine A(3) receptors, i.e. N-6-(3-iodobenzyl)adenosine-5'-N-methyluronamide, did not induce such effects. Because 5-fluorouracil is a cell cycle-specific drug damaging mainly cells in the S-phase. protective effects of CPA can be explained by its inhibitory action on the cell cycling. This interpretation was confirmed by experiments demonstrating that repeated administration of CPA in the hyperproliferation phase of the recovering haematopoiesis after 5-fluorouracil treatment inhibited transiently restoration of CFC-GM counts. (C) 2004 Elsevier B.V. All rights reserved.