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连续四年分析纳米颗粒暴露工人个体 DNA 甲基化模式变化。

Individual DNA Methylation Pattern Shifts in Nanoparticles-Exposed Workers Analyzed in Four Consecutive Years.

机构信息

Department of Genetic Toxicology and Epigenetics, Institute of Experimental Medicine CAS, Videnska 1083, 142 20 Prague 4, Czech Republic.

Department of Occupational Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Na Bojisti 1, 120 00 Prague 2, Czech Republic.

出版信息

Int J Mol Sci. 2021 Jul 22;22(15):7834. doi: 10.3390/ijms22157834.

Abstract

A DNA methylation pattern represents an original plan of the function settings of individual cells and tissues. The basic strategies of its development and changes during the human lifetime are known, but the details related to its modification over the years on an individual basis have not yet been studied. Moreover, current evidence shows that environmental exposure could generate changes in DNA methylation settings and, subsequently, the function of genes. In this study, we analyzed the effect of chronic exposure to nanoparticles (NP) in occupationally exposed workers repeatedly sampled in four consecutive years (2016-2019). A detailed methylation pattern analysis of 14 persons (10 exposed and 4 controls) was performed on an individual basis. A microarray-based approach using chips, allowing the assessment of more than 850 K CpG loci, was used. Individual DNA methylation patterns were compared by principal component analysis (PCA). The results show the shift in DNA methylation patterns in individual years in all the exposed and control subjects. The overall range of differences varied between the years in individual persons. The differences between the first and last year of examination (a three-year time period) seem to be consistently greater in the NP-exposed subjects in comparison with the controls. The selected 14 most differently methylated cg loci were relatively stable in the chronically exposed subjects. In summary, the specific type of long-term exposure can contribute to the fixing of relevant epigenetic changes related to a specific environment as, e.g., NP inhalation.

摘要

DNA 甲基化模式代表了个体细胞和组织功能设置的原始计划。其在人类一生中的发展和变化的基本策略是已知的,但关于其在个体基础上多年来的修饰的细节尚未得到研究。此外,现有证据表明,环境暴露可能会导致 DNA 甲基化设置的变化,进而导致基因功能的变化。在这项研究中,我们分析了职业暴露工人在连续四年(2016-2019 年)中反复采样时慢性暴露于纳米颗粒(NP)的影响。对 14 人(10 名暴露者和 4 名对照者)进行了个体基础上的详细甲基化模式分析。使用微阵列芯片的方法,允许评估超过 850 K CpG 位点。通过主成分分析(PCA)比较个体 DNA 甲基化模式。结果显示,所有暴露者和对照者的个体年中 DNA 甲基化模式都发生了变化。个体人之间的差异范围在不同年份有所不同。与对照组相比,NP 暴露组在第一次和最后一次检查(三年时间)之间的差异似乎始终更大。在慢性暴露的受试者中,选定的 14 个甲基化差异最大的 cg 位点相对稳定。总之,特定类型的长期暴露可能会导致与特定环境(例如 NP 吸入)相关的相关表观遗传变化固定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2259/8346047/c340b22165ac/ijms-22-07834-g0A1.jpg

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