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  • Title: Selectivity of action of 5-FU: biochemical basis.
    Author: Rustum YM, Danhauser L, Wang G.
    Journal: Bull Cancer; 1979; 66(1):43-7. PubMed ID: 154352.
    Abstract:
    Studies have been initiated to investigate the biochemical basis for selectivity of action of 5-fluorouracil against tumor cells. These studies included the measurement of 5-fluorodeoxyuridine monophosphate pools and the amount of 5-fluorouracil incorporated into RNA at various times following the administration of labeled 5-fluorouracil-6-3H, 5-fluorouridine-6-3H and 5-fluorodeoxyuridine-6-3H to animals bearing sensitive L1210 cells and L1210 resistant to 5-fluorouracil. The data indicate that: 1) in both cell lines the order of drug uptake into cells in vivo was in the order of fluorouride greater than fluorouracil greater then fluorodeoxyuridine; 2) there was no qualitative difference between the two cell lines in term of the extent of drug activation; 3) the data suggest a strong correlation between the amount of 5-fluorodeoxyuridine-monophosphates formed and retained at the target site and responsiveness to these agents. The effects of thymidine administered by continuous infusion and i.v. bolus injection on the antitumor activity of 5-fluorouracil was also investigated in animals bearing the induced colon carcinoma. The data suggest that thymidine, in combination with 5-fluorouracil, improves the therapeutic index of 5-fluorouracil. Initial studies on the metabolism of 5-fluorouracil in patients bearing the colon carcinoma are also reported herein.
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