Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Int J Mol Sci. 2021 Feb 27;22(5):2378. doi: 10.3390/ijms22052378.
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.
细胞和动物研究均表明，蛋氨酸的完全或部分缺乏会抑制肿瘤生长。因此，这种营养干预的潜在应用最近对癌症患者的治疗产生了极大的兴趣。不幸的是，饮食改变也会影响健康的免疫细胞，如单核细胞/巨噬细胞及其骨髓前体细胞。由于约一半的癌症患者接受放疗，因此需要评估饮食中蛋氨酸缺乏对放疗前和/或放疗后免疫细胞的潜在有害影响。因此，我们通过在蛋氨酸缺乏或补充培养基中培养 1 个月后的染色体分析，研究了蛋氨酸含量的调节是否会改变体外鼠 RAW 264.7 单核细胞/巨噬细胞系的遗传稳定性。我们还分析了用蛋氨酸缺乏或补充饮食喂养 2 个月的 CBA/J 小鼠骨髓细胞中的染色体畸变。虽然所有 RAW 264.7 细胞均显示涉及三条染色体的复杂易位，但根据染色体 9 的带型鉴定出三个不同的克隆。蛋氨酸缺乏改变了三个克隆的比例，并增加了 RAW 264.7 中的染色体畸变和 DNA 损伤。蛋氨酸缺乏还增加了 RAW 264.7 细胞中辐射诱导的染色体畸变和 DNA 损伤。此外，维持在蛋氨酸缺乏饮食中的小鼠的骨髓细胞中出现的染色体畸变比给予蛋氨酸充足或补充饮食的小鼠更多。这些发现表明，在常规癌症治疗中同时实施蛋氨酸缺乏饮食时需要谨慎。
