Impact of schedule on leucovorin potentiation of fluorouracil antitumor activity in dietary folic acid deplete mice

Biochemical Pharmacology
K RaghunathanDavid G Priest

Abstract

A dietary folic acid depleted mouse model was established and used to evaluate the relationship between elevation of reduced folates after leucovorin (LV) administration and potentiation of fluorouracil (FU) response of an implanted tumor. C3H mouse mammary adenocarcinomas from mice maintained on a folic acid deplete diet had modestly decreased methylenetetrahydrofolate and tetrahydrofolate levels, and were somewhat less responsive to FU alone compared with replete animals. LV administration resulted in a substantial increase in tumor folate by 1 hr that returned to near basal levels by 12 hr. Reduced folates were elevated to a lesser extent in animals on a standard diet. Tumor growth was suppressed approximately 80% when FU was administered to depleted animals 1 hr after LV administration, compared with approximately 50% suppression in control mice. LV administered 12 hr before FU resulted in tumor growth stimulation that was consistent with the pronounced growth stimulation when LV was administered without FU. These results show that dietary folic acid depletion can lead to a more responsive FU/LV model and that administration of LV at an improper time before FU not only can fail to potentiate but also can result in tumor gro...Continue Reading

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Citations

Aug 24, 2000·International Journal of Cancer. Journal International Du Cancer·H H BackusG J Peters
Jul 29, 2009·Cancer Chemotherapy and Pharmacology·Sotaro SadahiroToshinori Oka
Aug 11, 2010·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Rebecca S HolmesUNKNOWN Colon Cancer Family Registry
Aug 17, 1999·Biochemical Pharmacology·K Raghunathan, D G Priest
May 15, 2004·Nutrition Reviews·Martin A WhitesideGary L Johanning

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