SELECTIVE EXPANSION OF 5,10-METHYLENETETRAHYDROFOLATE POOLS AND MODULATION OF 5-FLUOROURACIL ANTITUMOR-ACTIVITY BY LEUCOVORIN INVIVO

  • 15 May 1989
    • journal article
    • research article
    • Vol. 49  (10) , 2592-2596
Abstract
Expansion of CH2THF pools in tissues of BALB/c mice bearing s.c.-implanted EMT6 mammary adenocarcinomas was measured after leucovorin administration. Twenty-four mice were treated with leucovorin at doses of 0, 45, 90, or 180 mg/kg/injection .times. 8 injections spaced over 48 h. Tumor and bone marrow cytosols were assayed for CH2THF by forming ternary complexes with thymidylate synthase and [3H]dFdUMP. Tumor CH2THF pools were expanded significantly at the two higher doses. Marrow levels were not different from controls. Groups of tumor bearing mice were treated with saline, leucovorin, 5-fluorouracil or 5-fluourouracil plus leucovorin on an optimal dosage schedule. Measured from the last day of treatment, these tumors grew to 10 mm root-mean square diameters in 3.5 .+-. 1.4, 5.0 .+-. 1.2, 6.5 .+-. 1.5, and 9.3 .+-. 1.2 days, respectively. Growth rates were significantly different from controls only in the latter two groups.

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