纳米材料表观遗传学效应的研究进展

Research advances in epigenetic effect induced by nanomaterials

随着纳米科技的发展和纳米材料的广泛应用,人们暴露于纳米材料的机会日益增多,对其所引起的表观遗传学效应的研究也逐渐增多。纳米材料介导的体外表观遗传学效应与其种类、性质和处理条件等有关。纳米银可使细胞基因组整体甲基化水平升高且具有浓度效应关系;氧化锌、氧化钛和结晶型二氧化硅纳米颗粒会降低基因组整体甲基化水平;碳纳米管(NT)仅发现有特异基因甲基化作用。同时,DNA甲基化酶的水平也受纳米材料影响。纳米材料介导的组蛋白修饰作用多为乙酰化和磷酸化,并受到其电荷和存在状态(晶体,非晶体)的影响。对于纳米材料诱导的微RNA(miRNA)表达变化的研究,多采用高通量方法,差异表达的miRNA结果异质性大,且会受到纳米材料粒径、表面电荷、处理时间和浓度的影响。在体实验仅有纳米材料介导的甲基化和miRNA表达水平相关的研究,且多为长期重复暴露实验,除与体外实验结果相似外,还发现了纳米材料所致甲基化水平改变具有可逆性和组织特异性,对幼龄大鼠和(或)小鼠的效应更强。尽管近年来发表了许多有关纳米材料表观遗传学效应的研究,但有些结果还不确定,其是否具有可遗传性仍有待研究。本文综述了纳米材料对DNA甲基化、组蛋白修饰和miRNA表达水平的影响,希望能为纳米材料表观遗传学效应的研究提供参考。

With the development of nanotechnology and the wide application of nanomaterials(NM),people are increasingly exposed to NM and the study on the epigenetic effects induced by such exposure has also gradually increased.Epigenetic effects induced by NM are related to the material type and material property as well as processing conditions of NM.Silver nanoparticles(NPs)can increase the genome-wide DNA methylation level of cells and have a dose-effect relationship.ZnO2-NP,TiO2-NP,and crystalline SiO2-NP can decrease the genome-wide DNA methylation level.Only specific gene promoter methylation is found following carbon nanotube treatment.At the same time,the expression level of DNA methylase transferase is also affected by NM.NM-induced histone modification is mostly acetylated and phosphorylated,which is affected by the charge and existence state(crystal,amorphous)of NM.High-throughput methods are used for the study of micro RNA(mi RNA)expression levels induced by NM.The differentially expressed miRNA results are heterogeneous and will be affected by NP size,surface charge,treatment time and concentration.In In vivo experiments,only methylation and mi RNA expression levels induced by NM have been studied and they are mostly long-term repeated exposure experiments.Besides the similar result found in in vitro experiments,it is also found that the DNA methylation level caused by NM is reversible,tissue specific and the effect on young mice is stronger.Although many studies related to the epigenetics of NM have been published in recent years,some results are still uncertain,and whether it is heritable remains to be studied.This paper summarizes the related studies,involving the effects of NM on DNA methylation,histone modification,and mi RNA expression levels and we hope to provide reference for the study of the epigenetic effects induced by NM.