Mechanism of diethyldithiocarbamate modulation of murine bone marrow toxicity.
Sodium diethyldithiocarbamate (DDTC) has been shown to modulate the myelosuppression that commonly occurs following treatment with anticancer drugs in mice. In order to investigate the mechanism of action of this myeloprotector, murine long-term bone marrow cultures were treated with DDTC alone or were preceded by the anticancer drug cis-diammine(cyclobutanedicarboxylato)platinum(II) (CBDCA), and the granulocyte/macrophage colony-stimulating activity of the supernatants was measured. The supernatants harvested from DDTC-treated cultures enhanced proliferation of granulocyte/macrophage progenitor cells almost 4-fold compared to cultures treated with no drug or with CBDCA alone. Pretreatment of cultures with CBDCA neither enhanced nor inhibited DDTC-induced colony-stimulating activity. Similar results were obtained by using marrow stromal cell cultures free of hematopoietic cells. Thus, DDTC may hasten bone marrow recovery by augmenting stromal cell production of a factor(s) with hematopoietic colony-stimulating activity.
Schmalbach
T K
TK
Department of Pharmacology, University of Rochester School of Medicine and Dentistry, New York 14642.
Borch
R F
RF
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D016190:Carboplatin; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D004050:Ditiocarb / Q000633:toxicity*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000378:metabolism*; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009944:Organoplatinum Compounds / Q000633:toxicity; D012485:Salmonella typhi
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D008070:Lipopolysaccharides; D009944:Organoplatinum Compounds; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004050:Ditiocarb; D016190:Carboplatin; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone