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端粒动态在人类和动物中的研究进展:环境毒理学的综述与展望。

Telomere dynamic in humans and animals: Review and perspectives in environmental toxicology.

机构信息

Department Chrono-Environnement, UMR UFC/CNRS 6249 USC INRA University of Bourgogne Franche-Comté, 16 route de Gray, 25000 Besançon, France.

TESORA, Le Visium, 22 avenue Aristide Briand, 94110 Arcueil, France.

出版信息

Environ Int. 2019 Oct;131:105025. doi: 10.1016/j.envint.2019.105025. Epub 2019 Jul 25.

Abstract

Telomeres (TLs) play major roles in stabilizing the genome and are usually shortened with ageing. The maintenance of TLs is ensured by two mechanisms involving telomerase (TA) enzyme and alternative lengthening telomeres (ALT). TL shortening and/or TA inhibition have been related to health effects on organisms (leading to reduced reproductive lifespan and survival), suggesting that they could be key processes in toxicity mechanisms (at molecular and cellular levels) and relevant as an early warning of exposure and effect of chemicals on human health and animal population dynamics. Consequently, a critical analysis of knowledge about relationships between TL dynamic and environmental pollution is essential to highlight the relevance of TL measurement in environmental toxicology. The first objective of this review is to provide a survey on the basic knowledge about TL structure, roles, maintenance mechanisms and causes of shortening in both vertebrates (including humans) and invertebrates. Overall, TL length decreases with ageing but some unexpected exceptions are reported (e.g., in species with different lifespans, such as the nematode Caenorhabditis elegans or the crustacean Homarus americanus). Inconsistent results reported in various biological groups or even between species of the same genus (e.g., the microcrustacean Daphnia sp.) indicate that the relation usually proposed between TL shortening and a decrease in TA activity cannot be generalized and depends on the species, stage of development or lifespan. Although the scientific literature provides evidence of the effect of ageing on TL shortening, much less information on the relationships between shortening, maintenance of TLs, influence of other endogenous and environmental drivers, including exposure to chemical pollutants, is available, especially in invertebrates. The second objective of this review is to connect knowledge on TL dynamic and exposure to contaminants. Most of the studies published on humans rely on correlative epidemiological approaches and few in vitro experiments. They have shown TL attrition when exposed to contaminants, such as polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls (PCB), pesticides and metallic elements (ME). In other vertebrates, the studies we found deals mainly with birds and, overall, report a disturbance of TL dynamic consecutively to exposure to chemicals, including metals and organic compounds. In invertebrates, no data are available and the potential of TL dynamic in environmental risk assessment remains to be explored. On the basis of the main gaps identified some research perspectives (e.g., impact of endogenous and environmental drivers, dose response effects, link between TL length, TA activity, longevity and ageing) are proposed to better understand the potential of TL and TA measurements in humans and animals in environmental toxicology.

摘要

端粒(TLs)在稳定基因组方面发挥着重要作用,通常随着年龄的增长而缩短。TLs 的维持是通过涉及端粒酶(TA)酶和替代延长端粒(ALT)的两种机制来保证的。TL 缩短和/或 TA 抑制与生物体的健康影响有关(导致生殖寿命和存活率降低),这表明它们可能是毒性机制(在分子和细胞水平上)的关键过程,并作为对化学物质暴露和对人类健康和动物种群动态影响的早期预警具有相关性。因此,对 TL 动态与环境污染之间关系的知识进行批判性分析至关重要,以突出 TL 测量在环境毒理学中的相关性。本综述的第一个目标是提供关于 TL 结构、作用、维持机制以及脊椎动物(包括人类)和无脊椎动物中缩短的原因的基本知识概述。总的来说,TL 长度随着年龄的增长而缩短,但也有一些意外的例外情况(例如,在寿命不同的物种中,如线虫秀丽隐杆线虫或甲壳纲动物美洲螯龙虾)。在不同的生物群体中报告的不一致结果,甚至在同一属的物种之间(例如,微型甲壳类动物溞属),表明通常提出的 TL 缩短与 TA 活性降低之间的关系不能一概而论,并且取决于物种、发育阶段或寿命。尽管科学文献提供了衰老对 TL 缩短的影响的证据,但关于 TL 缩短、TL 维持之间的关系、其他内源性和环境驱动因素的影响的信息较少,包括暴露于化学污染物,尤其是在无脊椎动物中。本综述的第二个目标是将 TL 动态与暴露于污染物的知识联系起来。发表在人类身上的大多数研究都依赖于相关性流行病学方法,而很少进行体外实验。它们表明,当暴露于多环芳烃(PAH)、多氯联苯(PCB)、农药和金属元素(ME)等污染物时,TL 会磨损。在其他脊椎动物中,我们发现的研究主要涉及鸟类,总体上报告了化学物质暴露后 TL 动态的干扰,包括金属和有机化合物。在无脊椎动物中,没有可用的数据,TL 动态在环境风险评估中的潜力仍有待探索。根据确定的主要差距,提出了一些研究展望(例如,内源性和环境驱动因素的影响、剂量反应效应、TL 长度、TA 活性、寿命和衰老之间的联系),以更好地理解 TL 和 TA 测量在人类和动物环境毒理学中的潜力。

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