Response to 5-fluorouracil chemotherapy is modified by dietary folic acid deficiency in Apc(Min/+) mice.
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.
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017931:DNA Primers / Q000737:chemistry; D004032:Diet; D005472:Fluorouracil / Q000627:therapeutic use*; D005492:Folic Acid / Q000008:administration & dosage; D005494:Folic Acid Deficiency / Q000503:physiopathology*; D017491:Genes, APC / Q000502:physiology; D007414:Intestinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction
D000964:Antimetabolites, Antineoplastic; D017931:DNA Primers; D005492:Folic Acid; D005472:Fluorouracil