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.
Highlights
Methionine is an essential sulfur-containing amino acid that regulates a number of key cellular functions, including, but not limited to, protein synthesis, methylation of both DNA and RNA, and generation of polyamines [1]
We provide a cytogenetic characterization of the mouse RAW
G-banding permits the identification of a change in the banding pattern, indicating chromosomal rearrangements/translocations
Summary
Methionine is an essential sulfur-containing amino acid that regulates a number of key cellular functions, including, but not limited to, protein synthesis (as the first amino acid of all newly synthesized polypeptide chains), methylation of both DNA and RNA, and generation of polyamines [1]. Because methionine regulates a variety of key cellular functions, tumor control with complete or partial deficiency of dietary methionine has been a major focus of research for decades. While a large number of in vitro and preclinical studies demonstrate that dietary methionine deficiency inhibits tumor growth [2,3,4], the clinical success of this strategy is not well-established. Monocytes circulate in the blood for around 1 day and, during this time, some of the circulating monocytes infiltrate into various tissues for immune surveillance, where they subsequently differentiate into macrophages or microglia when they present in the brain
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