Dietary methionine deficiency enhances genetic instability in murine immune cells

Regina L. Binz, Ratan Sadhukhan, Isabelle R. Miousse, Sarita Garg, Igor Koturbash, Daohong Zhou, Martin Hauer-Jensen, Rupak Pathak

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Both cell and animal studies have shown that complete or partial deficiency of methionine inhibits tumor growth. Consequently, the potential implementation of this nutritional intervention has recently been of great interest for the treatment of cancer patients. Unfortunately, diet alteration can also affect healthy immune cells such as monocytes/macrophages and their precursor cells in bone marrow. As around half of cancer patients are treated with radiotherapy, the potential deleterious effect of dietary methionine deficiency on immune cells prior to and/or following irradiation needs to be evaluated. Therefore, we examined whether modulation of methionine content alters genetic stability in the murine RAW 264.7 monocyte/macrophage cell line in vitro by chromosomal analysis after 1-month culture in a methionine-deficient or supplemented medium. We also analyzed chromosomal aberrations in the bone marrow cells of CBA/J mice fed with methionine-deficient or supplemented diet for 2 months. While all RAW 264.7 cells revealed a complex translocation involving three chromosomes, three different clones based on the banding pattern of chromosome 9 were identified. Methionine deficiency altered the ratio of the three clones and increased chromosomal aberrations and DNA damage in RAW 264.7. Methionine deficiency also increased radiation-induced chromosomal aberration and DNA damage in RAW 264.7 cells. Furthermore, mice maintained on a methionine-deficient diet showed more chromosomal aberrations in bone marrow cells than those given methionine-adequate or supplemented diets. These findings suggest that caution is warranted for clinical implementation of methionine-deficient diet concurrent with conventional cancer therapy.

Original languageEnglish (US)
Article number2378
Pages (from-to)1-13
Number of pages13
JournalInternational journal of molecular sciences
Volume22
Issue number5
DOIs
StatePublished - Mar 1 2021
Externally publishedYes

Keywords

  • Chromosomal instability
  • DNA damage and repair
  • G-banding
  • Macrophages
  • Monocytes
  • Radiation
  • Spectral karyotyping

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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