Selective expansion of 5,10-methylenetetrahydrofolate pools and modulation of 5-fluorouracil antitumor activity by leucovorin in vivo.

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 x 8 injections spaced over 48 h. Tumor and bone marrow cytosols were assayed for CH2THF by forming ternary complexes with thymidylate synthase and [3H]FdUMP. 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 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.

• Authors: J E Wright, A Dreyfuss, I el-Magharbel, D Trites, S M Jones, S A Holden, A Rosowsky, E Frei 3rd
• Journal: Cancer research (Cancer Res) Vol. 49 Issue 10 Pg. 2592-6 (May 15 1989) ISSN: 0008-5472 [Print] United States
• PMID: 2785434 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Tetrahydrofolates
• 5,10-methylenetetrahydrofolic acid
• Fluorodeoxyuridylate
• Leucovorin
• Fluorouracil

Topics

• Animals
• Female
• Fluorodeoxyuridylate (metabolism)
• Fluorouracil (administration & dosage, metabolism, therapeutic use)
• Leucovorin (administration & dosage, pharmacology)
• Mammary Neoplasms, Experimental (drug therapy, metabolism)
• Mice
• Mice, Inbred BALB C
• Tetrahydrofolates (metabolism)