Response to 5-fluorouracil Chemotherapy Is Modified by Dietary Folic Acid Deficiency in Apc(Min/+) Mice

Cancer Lett. 2002 Dec 10;187(1-2):153-62. doi: 10.1016/s0304-3835(02)00402-0.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / physiopathology*
  • Intestinal Neoplasms / prevention & control*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Polymerase Chain Reaction


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