COMPARISON OF 5-FLUOROURACIL METABOLISM IN 2 HUMAN GASTROINTESTINAL TUMOR-CELL LINES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (3) , 909-914
Abstract
HuTu 80 and HT 29 are human gastrointestinal tumor cell lines which differ 20-fold in their sensitivity to growth inhibition by 5-fluorouracil (FUra). Thymidine reverses the growth inhibition produced by FUra in HT 29 cells but not in HuTu 80 cells. Futhermore, the presence of deoxyinosine potentiates. FUra action in HuTu 80 cells, while having no effect on growth inhibition by FUra in HT 29 cells. A comparison of FUra metabolism in the 2 cell lines, following a 24-h exposure of the cells to equitoxic concentrations of FUra, demonstrated that such exposure led to thymidylate synthetase inhibition in both HuTu 80 and HT 29 cells. This inhibition, however, was accompanied by a 6-fold greater level of incorporation of FUra into RNA in HuTu 80 cells than in HT 29 cells, and suggests that drug incorporation into RNA may be the dominant determinant of growth inhibition by FUra in HuTu 80 cells. Deoxyinosine, which potentiates FUra action in HuTu 80 cells, was found to alter FUra metabolism in the cells so that thymidylate synthetase inhibition was now achieved under conditions of reduced FUra incorporation into RNA. Thymidine was able to reverse growth inhibition of HuTu 80 cells by the FUra-deoxyinosine combination, suggesting a change in the mechanism of growth inhibition.

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