MECHANISM OF 5-FLUOROURIDINE TOXICITY IN NOVIKOFF HEPATOMA-CELLS

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 36  (11) , 4032-4038
Abstract
The mechanism of 5-fluorouridine (FUrd) cytotoxicity in Novikoff hepatoma cells varied under different experimental conditions. Continuous exposure to 1 .times. 10-7 M FUrd resulted in a simple thymineless death that could be prevented by the addition of 1 .times. 10-4 M thymidine to the culture medium. In contrast, 1 .times. 10-4 M thymidine did not prevent the growth inhibition caused by a 1-h exposure to 1 .times. 10-5 M FUrd, despite the fact that it did prevent the inhibition of DNA synthesis. Although it had no effect on the inhibition of DNA synthesis, 1 .times. 10-4 M uridine prevented the growth inhibition caused by a 1-h exposure to 1 .times. 10-5 M FUrd. Since 1 .times. 10-4 M uridine, but not 1 .times. 10-4 M thymidine, prevented the inhibition of rRNA maturation caused by a 1-h exposure to 1 .times. 10-5 M FUrd, apparently the effects of the analog on RNA metabolism contributed significantly to the cytotoxic activity of the analog in this specific experimental situation.