The importance of schedule on diethyldithiocarbamate modulation of drug-induced myelosuppression.
Sodium diethyldithiocarbamate (DDTC) has been investigated as a biochemical modulator of the toxicity associated with clinically used cancer chemotherapeutic agents. In the present study, we assessed the ability of DDTC to accelerate recovery of the granulocyte/macrophage progenitor cel (GM-CFC) population following treatment with the myelosuppressive drugs carboplatin (CBDCA), tetrachloro(d,1-trans)1,2-diaminocyclohexane platinum(IV) (tetraplatin), 5-fluorouracil (5-FU), and etoposide (VP-16) in B6D2F1 mice. Myelotoxicity was assessed 24 h after the injection of the anticancer drug using a GM-CFC clonogenic assay. In the case of all four anticancer drugs, the timing of DDTC administration appeared to be a critical parameter with regard to protection. A delay time of 1 h between the injection of the myelotoxic drug and treatment with DDTC (30 mg/kg) resulted in a significant reduction in cytotoxicity to GM-CFC, whereas a longer delay time did not. These results suggest that the timing of DDTC administration may be essential in modulating the myelosuppression associated with many chemotherapeutic regimens used in the clinic.
East
C J
CJ
Department of Pharmacology, University of Rochester School of Medicine and Dentistry, NY 14642.
Borch
R F
RF
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002470:Cell Survival / Q000187:drug effects; D004050:Ditiocarb / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D006098:Granulocytes / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D004050:Ditiocarb