收稿日期: 2024-11-10
录用日期: 2024-12-19
网络出版日期: 2025-04-21
基金资助
国家自然科学基金(81973062)
Advances in epigenetic mechanisms of lead toxicity
Received date: 2024-11-10
Accepted date: 2024-12-19
Online published: 2025-04-21
Supported by
National Natural Science Foundation of China(81973062)
铅是一种普遍存在于环境中的有毒重金属，也是人类历史上使用最早、应用最为广泛的重金属元素之一。由于铅在环境中不可降解，并且在人体内具有较长的生物累积效应（可长达30~50年），即使极低浓度的铅也能对人体造成健康损害，因而被世界卫生组织（World Health Organization，WHO）列为十大公共卫生关注化学品之一。铅进入人体后，通常会分布在脑、肝脏、肾脏、牙齿和骨骼等组织中，进而对全身各个系统、多种脏器和组织产生广泛的毒性作用。表观遗传学是研究基因表达在不改变核苷酸序列的情况下发生可遗传变化的学科，它揭示了基因表达修饰如何对细胞进行调控，导致具有相同DNA序列的细胞表现出不同形态与功能。尽管铅的毒性机制尚未完全明确，但近年来的研究表明，表观遗传学调控可能是铅毒性作用的重要机制之一。环境铅暴露可通过引发个体细胞的DNA甲基化、组蛋白修饰和微RNA（microRNA，miRNA）等表观遗传学改变，进而而诱发多种毒性反应。该文就铅毒性相关的表观遗传学机制研究现状，着重从DNA甲基化、组蛋白修饰和miRNA 3个方面进行综述，旨在从表观遗传学角度审视铅毒性，并为进一步探究铅的毒性机制提供理论基础。
张欣欣 , 颜崇淮 . 铅毒性的表观遗传学机制研究进展[J]. 上海交通大学学报（医学版）, 2025 , 45(4) : 500 -507 . DOI: 10.3969/j.issn.1674-8115.2025.04.013
Lead is a ubiquitous toxic heavy metal and one of the earliest and most widely used heavy metal elements in human history. Due to its non-degradable nature in the environment and its long biological accumulation effects (lasting up to 30‒50 years) in the human body, even trace amounts of lead can cause significant health damage. It has therefore been classified as one of the top ten public health concerns by the World Health Organization (WHO). Once absorbed into the body, lead is typically distributed in tissues such as the brain, liver, kidneys, teeth, and bones, thereby exerting widespread toxic effects on multiple organ systems. Epigenetics is the study of heritable changes in gene expression that occur without alterations in the nucleotide sequence. It reveals how modifications in gene expression regulate cellular functions, leading to diverse cellular phenotypes and functions despite identical DNA sequences. Although the toxic mechanisms of lead are not yet fully elucidated, recent studies suggest that epigenetic regulation may play a significant role in mediating lead toxicity. Environmental lead exposure can induce various epigenetic modifications in cells, such as DNA methylation, histone modifications, and microRNA (miRNA) alterations, which, in turn, can trigger multiple toxic responses. This paper presents a concise overview of current epigenetic investigations into lead toxicity, emphasizing DNA methylation, histone modifications, and miRNA dynamics. By adopting an epigenetic perspective, it offers a theoretical framework into understanding lead's toxic mechanisms comprehensively, facilitating further research in prevention and treatment strategies.
Key words： lead; DNA methylation (DNMT); histone modification; microRNA (miRNA)
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