The mechanism of 5-fluorouridine toxicity in Novikoff hepatoma cells.
The mechanism of 5-fluorouridine (FUrd) cytotoxicity in Novikoff hepatoma cells appears to vary under different experimental conditions. Continuous exposure to 1 X 10(-7) M FUrd results in a simple thymineless death that can be prevented by the addition of 1 X 10(-4) M thymidine to the culture medium. In contrast, 1 X 10(-4) M thymidine does not prevent the growth inhibition caused by a 1-hr exposure to 1 X 10(-5) M FUrd, despite the fact that it does prevent the inhibition of DNA synthesis. Although it has no effect on the inhibition of DNA synthesis, 1 X 10(-4) M uridine prevents the growth inhibition caused by a 1-hr exposure to 1 X 10(-5) M FUrd. Since 1 X 10(-4) M uridine, but not 1 X 10(-4) M thymidine, prevents the inhibition of ribosomal RNA maturation caused by a 1-hr exposure to 1 X 10(-5) M FUrd, it seems likely that the effects of the analog on RNA metabolism contribute significantly to the cytotoxic activity of the analog in this specific experimental situation.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003853:Deoxyribonucleosides / Q000378:metabolism; D003857:Deoxyuridine / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D013936:Thymidine / Q000494:pharmacology; D013997:Time Factors; D014529:Uridine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D003853:Deoxyribonucleosides; D012334:RNA, Neoplasm; D012335:RNA, Ribosomal; D006151:Guanosine; D013936:Thymidine; D003857:Deoxyuridine; D014529:Uridine