The effects of methyl-donor deficiency on the pattern of gene expression in mice

Colin D Glen, Laura E McVeigh, Mariel Voutounou, Yuri E Dubrova

Research output: Contribution to journalArticlepeer-review

Abstract

SCOPE: Hepatocellular carcinoma is one of the most frequently occurring cancers in humans. Recent human and animal studies have provided strong evidence for the effects of dietary deficiency of methyl donors on the development of liver cancer. However, the mechanisms underlying the effects of methyl-group deficiency on cancer risk are not properly understood.

METHODS AND RESULTS: Male BALB/c and CBA/Ca mice were maintained for 8 weeks on a synthetic diet lacking in choline and folic acid. Using microarrays, the pattern of gene expression was evaluated in their liver, kidney, and spleen. Methyl-donor deficient diet induced profound changes in gene expression in the liver of treated animals, whereas the effects of the methyl-deficient diet on the pattern of gene expression in the kidney and spleen were negligible. Methyl-donor dietary restriction induced strain-independent upregulation of genes involved in cellular proliferation in liver.

CONCLUSION: The results of our study provide a plausible explanation of why diets lacking methyl donors can induce the development of liver cancers in rodents and humans.

Original languageEnglish
Pages (from-to)501-6
Number of pages6
JournalMolecular Nutrition & Food Research
Volume59
Issue number3
DOIs
Publication statusPublished - Mar 2015

Keywords

  • Animals
  • Choline/pharmacology
  • Deficiency Diseases/genetics
  • Diet
  • Female
  • Folic Acid/pharmacology
  • Gene Expression Regulation/drug effects
  • Kidney/drug effects
  • Liver/drug effects
  • Liver Neoplasms/etiology
  • Male
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Spleen/drug effects
  • Tissue Array Analysis

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