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发展中国家的工业化与基因组不稳定风险增加:营养基因组学作为一种有前景的应对方法。

Industrialization and the increasing risk of genome instability in developing countries: nutrigenomics as a promising antidote.

作者信息

Anetor J I

机构信息

Department of Chemical Pathology, College of Medicine, University of Ibadan, Ibadan.

出版信息

Afr J Med Med Sci. 2010 Dec;39 Suppl:7-20.

Abstract

Increased reliance on chemicals in the industrializing developing countries places new demands on them, as they have limited resources to adequately regulate exposure to these chemicals. Majority of the chemicals cause mutation in DNA among others. The consequences of increased exposure to chemicals on the genome and their mitigation by Nutrigenomics, a science concerned with the prevention of genome damage by nutritional factors is poorly recognized in these countries. Growing evidence indicates that genome instability in the absence of overt exposure to genotoxicants is a sensitive marker of nutritional deficiency. Therefore, the increasing prevalence of chemicals in these countries which contribute to genome disturbances and the widespread nutritional deficiency, at least double the risk of genome instability.Environmental pollutants such polychlorobiphenyls, metal fumes, and fly ash, common in these countries are known to increase urinary level of 8-hydroxy deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, precursor of genome instability.Increasing evidence emphasizes the importance of zinc in both genetic stability and function. Zinc deficiency has been linked with oxidative stress, DNA damage and impairment of repair mechanisms as well as risk of cancer. Zinc plays an important role in vitamin A metabolism from which the retinoids are derived. Zinc is also an important component of the p53 protein, a DNA damage sensor which prevents genetic lesions contributing to genome instability.Zinc deficiency ranks among the top 10 leading causes of death in developing countries. A large proportion of the population in these countries ingests less than 50% of the RDA for Zn.This makes this genome protective nutrient among others grossly inadequate. Folate now also recognized for its role in genome stability, is among the nutrients frequently cited as critical to genome stability. Folate deficiency of sub- clinical degree is common. Reduced folate intake causes as much genome damage as that induced by exposure to a high dose of ionizing radiation. Even moderate folate deficiency causes very severe damage to the genome in the general population. All these accentuate the susceptibility of populations in these nations to environmental toxic assault requiring preventive measures employing the science of Nutrigenomics, probably augmented with adaptive response pathways such as the Nrf2 signaling pathway. Human populations in developing countries are increasingly exposed to a diverse array of industrial chemicals, which adversely modify the genome, the precursor of many diseases especially cancer. Nutrigenomics encompasses nutritional factors that protect the genome from damage and is a promising new field that can be exploited, perhaps augmented with the Nrf2 signaling pathway with international collaboration in these nations as an antidote to chemical-induced genome instability.

摘要

在工业化进程中的发展中国家,对化学品的依赖日益增加,这给它们带来了新的挑战,因为它们用于充分监管化学品接触的资源有限。大多数化学品会导致DNA发生突变等情况。在这些国家,人们对化学品接触增加对基因组的影响以及营养基因组学(一门关注通过营养因素预防基因组损伤的科学)对其的缓解作用认识不足。越来越多的证据表明,在没有明显接触基因毒性物质的情况下,基因组不稳定是营养缺乏的一个敏感指标。因此,这些国家中导致基因组紊乱的化学品日益普遍,加上普遍存在的营养缺乏,至少使基因组不稳定的风险增加了一倍。这些国家常见的环境污染物,如多氯联苯、金属烟雾和飞灰,已知会增加尿中8 - 羟基脱氧鸟苷(8 - OHdG)的水平,8 - OHdG是氧化DNA损伤的标志物,也是基因组不稳定的先兆。越来越多的证据强调了锌在遗传稳定性和功能方面的重要性。锌缺乏与氧化应激、DNA损伤、修复机制受损以及癌症风险有关。锌在维生素A代谢中起着重要作用,视黄醇类物质由此衍生而来。锌也是p53蛋白的重要组成部分,p53蛋白是一种DNA损伤传感器,可防止导致基因组不稳定的基因损伤。锌缺乏位列发展中国家十大主要死因之中。这些国家很大一部分人口摄入的锌量不到推荐膳食摄入量(RDA)的50%。这使得这种对基因组有保护作用的营养素以及其他营养素严重不足。叶酸现在也因其在基因组稳定性中的作用而受到认可,是经常被提及对基因组稳定性至关重要的营养素之一。亚临床程度的叶酸缺乏很常见。叶酸摄入量减少所导致的基因组损伤与高剂量电离辐射所引起的损伤一样多。即使是中度叶酸缺乏,也会对普通人群的基因组造成非常严重的损伤。所有这些都凸显了这些国家人群对环境毒性攻击的易感性,需要采取预防措施,运用营养基因组学这门科学,可能还需借助如Nrf2信号通路等适应性反应途径。发展中国家的人群越来越多地接触到各种各样的工业化学品,这些化学品会对基因组产生不利影响,而基因组是许多疾病尤其是癌症的先兆。营养基因组学涵盖了保护基因组免受损伤的营养因素,是一个有前景的新领域,可以加以利用,或许还可借助Nrf2信号通路,并通过这些国家的国际合作,作为对抗化学物质诱导的基因组不稳定的解药。

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