Effect of cis-diamminedichloroplatinum on erythropoietin production and hematopoietic progenitor cells.
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.
D000328:Adult; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004921:Erythropoietin / Q000096:biosynthesis*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D009336:Necrosis / Q000139:chemically induced; D051381:Rats
D004921:Erythropoietin; D002945:Cisplatin