The influence of folate and methionine on intestinal tumour development in the Apc Min/+ mouse model

Arnida Hani Teh, Erin Symonds, Caroline Bull, Peter Clifton, Michael Fenech

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Folate and methionine are critical for one-carbon metabolism impacting DNA synthesis, repair, and methylation processes, as well as polyamine synthesis. These micronutrients have been implicated in colorectal cancer risk. There are, however, inconsistencies within the literature, with some studies showing restriction to have tumour-inhibitory effects, whereas others suggest excess to have adverse outcomes. We conducted a review of the published data to examine the accumulated evidence for involvement of dietary folate and/or methionine restriction or excess in intestinal tumour development in the Apc Min/+ mouse model, which is genetically prone to develop such cancers. Thirteen publications were selected for evaluation based on the following inclusion criteria: (i) use of Apc Min/+ mouse model; (ii) interventions using dietary folate and/or methionine; and (iii) primary outcome measures focused on intestinal tumour development. We found that nutritional modulation of folate and methionine was shown to have different effects on intestinal cancer in the Apc Min/+ mouse, depending on the dosage, duration and timing of intervention, and interaction of the Apc Min/+ genotype with other genetic factors affecting folate and DNA methylation metabolism. Although some studies showed that folate deficiency before tumorigenesis tended to increase risk of tumour formation, there are inconsistencies regarding whether excess folate post-weaning or after tumour initiation increases intestinal tumour burden. Altogether, the pooled data do not appear to indicate a difference in effect on intestinal tumour incidence between post-weaning diets that are folate deficient or folate adequate. The Apc Min/+ mouse is a useful model for assessment of the impact of dietary folate on intestinal tumour development, but further research is required to understand the reasons for these inconsistencies amongst studies based on likely mechanisms, including modulation of nucleotide synthesis, DNA methylation, and chromosomal instability, which may affect the rate of cellular division and its control.

Original languageEnglish
Pages (from-to)64-75
Number of pages12
JournalMutation Research - Reviews in Mutation Research
Volume751
Issue number1
DOIs
Publication statusPublished - Jul 2012

Fingerprint

Folic Acid
Methionine
Neoplasms
DNA Methylation
Weaning
Intestinal Neoplasms
Chromosomal Instability
Micronutrients
Polyamines
Tumor Burden
DNA Repair
Publications
Colorectal Neoplasms
Carcinogenesis
Carbon
Nucleotides
Genotype
Outcome Assessment (Health Care)
Diet
Incidence

Keywords

  • Folate
  • Intestinal cancer
  • Methionine, Apc

ASJC Scopus subject areas

  • Genetics
  • Health, Toxicology and Mutagenesis

Cite this

The influence of folate and methionine on intestinal tumour development in the Apc Min/+ mouse model. / Teh, Arnida Hani; Symonds, Erin; Bull, Caroline; Clifton, Peter; Fenech, Michael.

In: Mutation Research - Reviews in Mutation Research, Vol. 751, No. 1, 07.2012, p. 64-75.

Research output: Contribution to journalArticle

Teh, Arnida Hani ; Symonds, Erin ; Bull, Caroline ; Clifton, Peter ; Fenech, Michael. / The influence of folate and methionine on intestinal tumour development in the Apc Min/+ mouse model. In: Mutation Research - Reviews in Mutation Research. 2012 ; Vol. 751, No. 1. pp. 64-75.
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