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染色体损伤与血液疾病和微量营养素状况相关联的研究

Association of chromosome damage detected as micronuclei with hematological diseases and micronutrient status.

机构信息

Nutrition and Metabolism Center, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.

出版信息

Mutagenesis. 2011 Jan;26(1):57-62. doi: 10.1093/mutage/geq081.

Abstract

Epidemiological studies reveal strong association between micronutrient deficiencies and development of cancer. Since chromosome breaks and abnormal chromosome segregation, identified as micronuclei (MN), are central to malignant transformation, the influence of micronutrient status upon MN frequency has been the subject of intense research. Motivating this effort is the idea that marginal micronutrient deficiencies lead to allocation of scarce cellular resources towards immediate survival at the expense of maintaining genomic integrity, placing the individual at greater risk for degenerative diseases and cancer in old age. The challenge in identifying an association between individual micronutrients and MN frequency stems from the complexity of human diet, simultaneous presence of multiple micronutrient deficiencies, variable genetic susceptibility and methodological difficulties. A unique model for studying MN in humans is provided by a group of haematological diseases, the chronic haemolytic anaemias associated with high reticulocyte count and absence of splenic function. These disorders may prove valuable for assessing the influence of micronutrient status once the effect of abnormal erythropoiesis on MN formation is adequately understood. Eventually, large population-based studies that can account for the baseline variability in MN frequency, lifestyle and genetic factors may be needed to uncover the DNA-damaging effect of poor diet. Understanding the link between micronutrient status and MN frequency will contribute towards determining optimal micronutrient intake to preserve long-term health.

摘要

流行病学研究揭示了微量营养素缺乏与癌症发展之间的强烈关联。由于染色体断裂和异常染色体分离,即微核(MN),是恶性转化的核心,因此,微量营养素状态对 MN 频率的影响一直是研究的热点。推动这一研究的理念是,边缘微量营养素缺乏会导致稀缺的细胞资源分配,以牺牲维持基因组完整性为代价,为个体在老年时患上退行性疾病和癌症带来更大的风险。在确定个体微量营养素和 MN 频率之间的关联时,面临的挑战源于人类饮食的复杂性、多种微量营养素缺乏的同时存在、遗传易感性的变化以及方法学上的困难。一组血液疾病为研究人类 MN 提供了独特的模型,这些疾病与高网织红细胞计数和脾脏功能缺失相关的慢性溶血性贫血。一旦充分了解异常红细胞生成对 MN 形成的影响,这些疾病可能对评估微量营养素状态的影响具有重要意义。最终,可能需要进行基于人群的大型研究,这些研究可以解释 MN 频率、生活方式和遗传因素的基线变异性,以揭示不良饮食对 DNA 损伤的影响。了解微量营养素状态和 MN 频率之间的联系将有助于确定最佳的微量营养素摄入以维持长期健康。

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