Interferon effects upon fluorouracil metabolism by HL-60 cells.
In order to better understand the synergistic antiproliferative effects of interferon in combination with fluorouracil (FUra), we studied effects of alpha 2-interferon upon FUra induced inhibition of thymidylate synthase of HL-60 cells. The 50% inhibitory dose for FUra decreased from approximately 75 microM to 10 microM following interferon treatment, as measured by whole cell activity assays. Enhanced FUra inhibition of cytosolic [3H] - FdUMP binding of interferon treated cells was also noted. FdUMP accumulation following FUra treatment increased over 10 fold in interferon treated cells, but dUMP did not increase. These results suggest that interferon can sensitize cells to FUra inhibition of thymidylate synthase by enhancing accumulation of FdUMP.
Department of Medicine and Cancer Center, University of New Mexico, School of Medicine, Albuquerque 87131.
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Elias
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Sandoval
D005472:Fluorouracil / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D011994:Recombinant Proteins; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*; D014542:Uridine Monophosphate / Q000378:metabolism
D007370:Interferon Type I; D011994:Recombinant Proteins; D014542:Uridine Monophosphate; D013940:Thymidylate Synthase; D005472:Fluorouracil