Effect of antabuse (disulfiram) on Rous sarcoma virus and on eukaryotic cells.
Antabuse (disulfiram) is widely used in the treatment of chronic alcoholism. We have examined the effect of this drug on malignant transformation by Rous sarcoma virus, on eukaryotic cell synthesis, and on nucleic acid binding. It was found that: (1) Disulfiram inhibits the activity of the RNA dependent DNA polymerase of Rous sarcoma virus and inactivates the ability of the virus to malignantly transform chick embryo cells. The monomer of disulfiram, diethyldithiocarbamate does not affect the virus. (2) Disulfiram induced the synthesis of four proteins in normal chick embryo and human foreskin cells. The monomer diethyldithiocarbamate, induced these proteins also. Cellular DNA synthesis is more sensitive to disulfiram than are RNA and protein synthesis. (3) Disulfiram binds to neither DNA or RNA in the presence or absence of copper. However, diethyldithiocarbamate in the presence of, but not in the absence of, copper binds to HeLa cell DNA and to Rous sarcoma virus 70 S genome RNA. These results indicate that this compound, which causes no symptoms in people who do not consume alcohol, may have significant effects on a cellular level.
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002478:Cells, Cultured; D002642:Chick Embryo; D003300:Copper / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D004221:Disulfiram / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology; D006801:Humans; D014176:Protein Biosynthesis; D012313:RNA / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors
D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D012313:RNA; D003300:Copper; D004247:DNA; D004050:Ditiocarb; D004221:Disulfiram