Myeloprotective effect of diethyldithiocarbamate treatment following 1,3-bis(2-chloroethyl)-1-nitrosourea, adriamycin, or mitomycin C in mice.
The effect of diethyldithiocarbamate (DDTC) on myelotoxicity induced by 1,3-bis(2-chloroethyl)-1-nitrosourea, Adriamycin, or mitomycin C in C57BL/6J x DBA/2J mice is reported here. All drugs were administered i.v. Myelotoxicity was assessed, 24 h after administration of the myelotoxic drug, using bone marrow stem cell (spleen colony-forming unit) and granulocyte/macrophage progenitor cell (granulocyte/macrophage colony-forming unit in culture) clonogenic assays. Administration of DDTC alone had no effect on spleen colony-forming units or granulocyte/macrophage colony-forming units in culture. 1,3-Bis(2-chloroethyl)-1-nitrosourea showed a dose-dependent toxicity for both cell types, and subsequent treatment with DDTC (300 mg/kg i.v. 3 h after 1,3-bis(2-chloroethyl)-1-nitrosourea) ameliorated this toxicity. The same dosing regimen of DDTC ameliorated Adriamycin-induced toxicity to bone marrow stem cells at the two higher doses tested. However, the myelosuppressive effects of mitomycin C were not altered by DDTC administration (300 mg/kg i.v. 3 h after or 30 min before mitomycin C). These results demonstrate that DDTC ameliorates myelotoxicity induced by several, but not all, chemotherapeutic agents and suggest a broad role for DDTC in cancer chemotherapy.
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*; D002330:Carmustine / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D004050:Ditiocarb / Q000494:pharmacology*; D004317:Doxorubicin / Q000633:toxicity*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D008297:Male; D051379:Mice; D016685:Mitomycin; D008937:Mitomycins / Q000633:toxicity*
D008937:Mitomycins; D016685:Mitomycin; D004317:Doxorubicin; D004050:Ditiocarb; D002330:Carmustine