Response to 5-fluorouracil chemotherapy is modified by dietary folic acid deficiency in Apc(Min/+) mice.

Abstract

5-Fluorouracil (5-FU) has been the foundation of advanced colorectal cancer treatment for over 40 years. The Apc(Min/+) mouse, which is genetically predisposed to intestinal neoplasia, was used to examine the effects of 5-FU in this system and the impact of dietary folic acid on those effects. 5-FU treatment resulted in a 60-80% reduction in tumor number. Clinically relevant toxicities, including myelosuppression and mucositis, are a part of this response. Tumor numbers rebounded completely following termination of 5-FU therapy, indicating that the drug inhibits tumor growth but does not eradicate them. In mice that were fed with a defined diet containing no folic acid (0 ppm), 5-FU not only induced regression of pre-existing tumors, but also inhibited tumor recovery following drug withdrawal. Our data indicate that a dietary folic acid deficiency, in promoting tumor regression and inhibiting tumor recovery, may enhance the therapeutic effects of 5-FU.

• Authors: Jody M Tucker, Celestia Davis, Maria E Kitchens, Marlene A Bunni, David G Priest, H Trent Spencer, Franklin G Berger
• Journal: Cancer letters (Cancer Lett) Vol. 187 Issue 1-2 Pg. 153-62 (Dec 10 2002) ISSN: 0304-3835 [Print] Ireland
• PMID: 12359363 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antimetabolites, Antineoplastic
• DNA Primers
• Folic Acid
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (therapeutic use)
• DNA Primers (chemistry)
• Diet
• Fluorouracil (therapeutic use)
• Folic Acid (administration & dosage)
• Folic Acid Deficiency (physiopathology)
• Genes, APC (physiology)
• Intestinal Neoplasms (genetics, metabolism, physiopathology, prevention & control)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Polymerase Chain Reaction