Hernández-Saavedra Diego, Strakovsky Rita S, Ostrosky-Wegman Patricia, Pan Yuan-Xiang
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Champaign, IL.
The Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Champaign, IL.
Adv Nutr. 2017 Nov 15;8(6):889-904. doi: 10.3945/an.117.016402. Print 2017 Nov.
The centromere is a genomic locus required for the segregation of the chromosomes during cell division. This chromosomal region together with pericentromeres has been found to be susceptible to damage, and thus the perturbation of the centromere could lead to the development of aneuploidic events. Metabolic abnormalities that underlie the generation of cancer include inflammation, oxidative stress, cell cycle deregulation, and numerous others. The micronucleus assay, an early clinical marker of cancer, has been shown to provide a reliable measure of genotoxic damage that may signal cancer initiation. In the current review, we will discuss the events that lead to micronucleus formation and centromeric and pericentromeric chromatin instability, as well transcripts emanating from these regions, which were previously thought to be inactive. Studies were selected in PubMed if they reported the effects of nutritional status (macro- and micronutrients) or environmental toxicant exposure on micronucleus frequency or any other chromosomal abnormality in humans, animals, or cell models. Mounting evidence from epidemiologic, environmental, and nutritional studies provides a novel perspective on the origination of aneuploidic events. Although substantial evidence exists describing the role that nutritional status and environmental toxicants have on the generation of micronuclei and other nuclear aberrations, limited information is available to describe the importance of macro- and micronutrients on centromeric and pericentromeric chromatin stability. Moving forward, studies that specifically address the direct link between nutritional status, excess, or deficiency and the epigenetic regulation of the centromere will provide much needed insight into the nutritional and environmental regulation of this chromosomal region and the initiation of aneuploidy.
着丝粒是细胞分裂过程中染色体分离所需的基因组位点。已发现这个染色体区域连同着丝粒周围区域易受损伤，因此着丝粒的扰动可能导致非整倍体事件的发生。构成癌症发生基础的代谢异常包括炎症、氧化应激、细胞周期失调等诸多方面。微核试验作为癌症的一种早期临床标志物，已被证明能可靠地衡量可能预示癌症发生的基因毒性损伤。在本综述中，我们将讨论导致微核形成以及着丝粒和着丝粒周围染色质不稳定的事件，以及此前被认为不活跃的这些区域产生的转录本。如果研究报告了营养状况（大量营养素和微量营养素）或环境毒物暴露对人类、动物或细胞模型中微核频率或任何其他染色体异常的影响，则在PubMed中进行筛选。来自流行病学、环境和营养研究的越来越多的证据为非整倍体事件的起源提供了新的视角。尽管有大量证据描述了营养状况和环境毒物在微核及其他核异常产生中的作用，但关于大量营养素和微量营养素对着丝粒和着丝粒周围染色质稳定性的重要性的信息却很有限。展望未来，专门研究营养状况、营养过剩或缺乏与着丝粒表观遗传调控之间直接联系的研究，将为该染色体区域的营养和环境调控以及非整倍体的起始提供急需的见解。
