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International Journal of Cell Cloning, Vol 3, 415-423, Copyright © 1985 by AlphaMed Press

ORIGINAL ARTICLES

Effect of cis-diamminedichloroplatinum on erythropoietin production and hematopoietic progenitor cells

SA Rothmann, P Paul, JK Weick, WR McIntyre and F Fantelli

Studies were conducted to determine whether the progressive development of anemia associated with the antineoplastic drug cis- diamminedichloroplatinum (cDDP) was the consequence of decreased erythropoietin (Epo) production due to cDDP-induced nephrotoxicity or selective inhibition of erythroid progenitor cells. Five days after a single intraperitoneal injection of cDDP, hypoxia-induced Epo production was not decreased in mice and was increased significantly in rats in spite of severe multifocal tubular necrosis. In both species, colony-forming units-granulocyte macrophage (CFU-gm) and colony-forming units-erythroid (CFU-e) were reduced significantly, with a greater decrease in CFU-e. Studies of an anemic patient receiving cDDP also showed elevated Epo and decreased CFU-gm and CFU-e. In vitro exposure of mouse and human bone marrow to cDDP caused a dose-dependent inhibition of CFU-gm and CFU-e in both species, with human CFU-e showing greatest sensitivity. The results indicate that the primary hematologic toxicity of cDDP is directed at the hematopoietic stem cell compartment.


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