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,l-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.