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不同类型环境颗粒物的体外毒性和表观遗传毒性

In Vitro Toxicity and Epigenotoxicity of Different Types of Ambient Particulate Matter.

作者信息

Miousse Isabelle R, Chalbot Marie-Cecile G, Pathak Rupak, Lu Xiaoyan, Nzabarushimana Etienne, Krager Kimberly, Aykin-Burns Nukhet, Hauer-Jensen Martin, Demokritou Philip, Kavouras Ilias G, Koturbash Igor

机构信息

*Department of Environmental and Occupational Health, Fay W. Boozman College of Public Health and.

Division of Radiation Health, Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205;

出版信息

Toxicol Sci. 2015 Dec;148(2):473-87. doi: 10.1093/toxsci/kfv200. Epub 2015 Sep 4.

Abstract

Exposure to ambient particulate matter (PM) has been associated with adverse health effects, including pulmonary and cardiovascular disease. Studies indicate that ambient PM originated from different sources may cause distinct biological effects. In this study, we sought to investigate the potential of various types of PM to cause epigenetic alterations in the in vitro system. RAW264.7 murine macrophages were exposed for 24 and 72 h to 5- and 50-μg/ml doses of the water soluble extract of 6 types of PM: soil dust, road dust, agricultural dust, traffic exhausts, biomass burning, and pollen, collected in January-April of 2014 in the area of Little Rock, Arkansas. Cytotoxicity, oxidative potential, epigenetic endpoints, and chromosomal aberrations were addressed. Exposure to 6 types of PM resulted in induction of cytotoxicity and oxidative stress in a type-, time-, and dose-dependent manner. Epigenetic alterations were characterized by type-, time-, and dose-dependent decreases of DNA methylation/demethylation machinery, increased DNA methyltransferases enzymatic activity and protein levels, and transcriptional activation and subsequent silencing of transposable elements LINE-1, SINE B1/B2. The most pronounced changes were observed after exposure to soil dust that were also characterized by hypomethylation and reactivation of satellite DNA and structural chromosomal aberrations in the exposed cells. The results of our study indicate that the water-soluble fractions of the various types of PM have differential potential to target the cellular epigenome.

摘要

暴露于环境颗粒物(PM)已被证明与包括肺部和心血管疾病在内的不良健康影响有关。研究表明,源自不同来源的环境PM可能会导致不同的生物学效应。在本研究中,我们试图在体外系统中研究各类PM引起表观遗传改变的可能性。将RAW264.7小鼠巨噬细胞暴露于2014年1月至4月在阿肯色州小石城地区收集的6种PM的水溶性提取物中,剂量分别为5μg/ml和50μg/ml,暴露时间为24小时和72小时。这6种PM分别是:土壤灰尘、道路灰尘、农业灰尘、交通尾气、生物质燃烧产物和花粉。我们研究了细胞毒性、氧化潜力、表观遗传终点以及染色体畸变情况。暴露于这6种PM会以类型、时间和剂量依赖的方式诱导细胞毒性和氧化应激。表观遗传改变的特征包括DNA甲基化/去甲基化机制的类型、时间和剂量依赖性降低,DNA甲基转移酶的酶活性和蛋白质水平升高,以及转座元件LINE-1、SINE B1/B2的转录激活和随后的沉默。暴露于土壤灰尘后观察到的变化最为明显,其特征还包括卫星DNA的低甲基化和重新激活以及暴露细胞中的结构染色体畸变。我们的研究结果表明,各类PM的水溶性部分对细胞表观基因组具有不同的靶向作用潜力。

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