ANTITUMOR MECHANISMS OF 3'-ETHYNYLURIDINE AND 3'-ETHYNYLCYTIDINE AS RNA-SYNTHESIS INHIBITORS - DEVELOPMENT AND CHARACTERIZATION OF 3'-ETHYNYLURIDINE-RESISTANT CELLS

To discover the mechanisms of anti-tumor action of 3'-ethynyluridine ( EUrd) and 3'-ethynylcytidine (ECyd), we established an EUrd-resistant variant from human fibrosarcoma HT-1080 cells. The cells were cross-re sistant to ECyd. Uridine/cytidine kinase activity diminished in the re sistant cells. The incorporation of EUrd and ECyd into the RNA fractio n in the resistant cells was less than that of the parental cells. EUr d-triphosphate inhibited RNA synthesis by human RNA polymerase II. The results led us to conclude that EUrd and ECyd are phosphorylated by u ridine/cytidine kinase to 5'-triphosphates, and that their triphosphat es might inhibit RNA polymerase. (C) 1997 Elsevier Science Ireland Ltd .