Suppr超能文献

从表观遗传学角度看环境毒物、退行性疾病的发病率及治疗方法。

Environmental toxicants, incidence of degenerative diseases, and therapies from the epigenetic point of view.

作者信息

Hodjat Mahshid, Rahmani Soheila, Khan Fazlullah, Niaz Kamal, Navaei-Nigjeh Mona, Mohammadi Nejad Solmaz, Abdollahi Mohammad

机构信息

Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.

Dental Research Center, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Arch Toxicol. 2017 Jul;91(7):2577-2597. doi: 10.1007/s00204-017-1979-9. Epub 2017 May 17.

Abstract

Epigenotoxicology is an emerging field of study that investigates the non-genotoxic epigenetic effects of environmental toxicants resulting in alteration of normal gene expression and disruption of cell function. Recent findings on the role of toxicant-induced epigenetic modifications in the development of degenerative diseases have opened up a promising research direction to explore epigenetic therapy approaches and related prognostic biomarkers. In this review, we presented comprehensive data on epigenetic alterations identified in various diseases, including cancer, autoimmune disorders, pulmonary conditions as well as cardiovascular, gastrointestinal and bone disease. Although data on abnormalities of DNA methylation and their role in the development of diseases are abundant, less is known about the impact of histone modifications and microRNA expressions. Further, we discussed the effects of selected common environmental toxicants on epigenetic modifications and their association with particular abnormalities. A number of different environmental toxicants have been identified for their role in aberrant DNA methylation, histone modifications, and microRNA expression. Such epigenetic effects were shown to be tissue-type specific and highly associated with the level and duration of exposure. Finally, we described present and future therapeutic strategies, including medicines and dietary compounds for combating the toxicant-induced epigenetic alterations. There are currently seven histone deacetylase inhibitors and two DNA methyltransferase inhibitors approved for clinical use and many other promising candidates are in preclinical and clinical testing. Dietary compounds are thought to be the effective and safe strategies for treating and prevention of epigenetic pathophysiological conditions. Still more concentrated epigenetic researches are required for evaluation of chemical toxicity and identifying the causal association between key epigenetic alteration and disease.

摘要

表观遗传毒理学是一个新兴的研究领域,它研究环境毒物的非基因毒性表观遗传效应,这种效应会导致正常基因表达改变和细胞功能紊乱。关于毒物诱导的表观遗传修饰在退行性疾病发展中的作用的最新发现,为探索表观遗传治疗方法和相关预后生物标志物开辟了一个有前景的研究方向。在这篇综述中,我们展示了在各种疾病中发现的表观遗传改变的综合数据,这些疾病包括癌症、自身免疫性疾病、肺部疾病以及心血管、胃肠道和骨骼疾病。虽然关于DNA甲基化异常及其在疾病发展中的作用的数据很多,但关于组蛋白修饰和微小RNA表达的影响却知之甚少。此外,我们讨论了选定的常见环境毒物对表观遗传修饰的影响及其与特定异常的关联。已确定多种不同的环境毒物在异常DNA甲基化、组蛋白修饰和微小RNA表达中起作用。这些表观遗传效应显示出组织类型特异性,并且与暴露水平和持续时间高度相关。最后,我们描述了当前和未来的治疗策略,包括用于对抗毒物诱导的表观遗传改变的药物和膳食化合物。目前有七种组蛋白去乙酰化酶抑制剂和两种DNA甲基转移酶抑制剂被批准用于临床,许多其他有前景的候选药物正在进行临床前和临床试验。膳食化合物被认为是治疗和预防表观遗传病理生理状况的有效且安全的策略。仍需要更集中的表观遗传学研究来评估化学毒性,并确定关键表观遗传改变与疾病之间的因果关系。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验