The importance of schedule on diethyldithiocarbamate modulation of drug-induced myelosuppression.

Abstract

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.

• Authors: C J East, R F Borch
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 31 Issue 2 Pg. 123-6 ( 1992) ISSN: 0344-5704 [Print] Germany
• PMID: 1333368 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Ditiocarb

Topics

• Animals
• Antineoplastic Agents (adverse effects)
• Cell Survival (drug effects)
• Ditiocarb (administration & dosage, adverse effects)
• Drug Administration Schedule
• Granulocytes (drug effects)
• Hematopoietic Stem Cells (drug effects)
• Macrophages (drug effects)
• Male
• Mice
• Tumor Stem Cell Assay