Early Epigenetic Responses in the Genomic DNA Methylation Fingerprints in Cells in Response to Sublethal Exposure of Silver Nanoparticles.
Early Epigenetic Responses in the Genomic DNA Methylation Fingerprints in Cells in Response to Sublethal Exposure of Silver Nanoparticles.
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DOI：
10.3389/fbioe.2022.927036
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发表时间：
2022
影响因子：
5.7
通讯作者：
Chen, Liqun
中科院分区：
文献类型：
--
作者：
Chen, Yue;Sheng, Fei;Wang, Xingyu;Zhang, Zhihong;Qi, Shiyong;Chen, Liqun
随着纳米技术和纳米科学的迅速发展，纳米安全性评价已引起公众的关注。尽管许多研究表明纳米材料可能导致遗传毒性，但在低剂量暴露下纳米材料对DNA甲基化的早期改变尚不完全清楚。在本研究中，我们研究了AgNPs对亚致死暴露下HEK 293 T细胞DNA甲基化指纹改变的潜在影响及其分子机制。有趣的是，银纳米颗粒处理增加了5-mC水平，并改变了甲基化相关酶的含量。从机制上讲，我们通过MeDIP-Seq和RNA-seq仔细检查了分子信号传导和生物学功能的变化。我们的研究结果表明，银纳米颗粒可能会破坏一些重要的调控网络，包括代谢过程，生物调节和其他细胞过程。更具体地说，在DNA甲基化指纹图中，有12个上调和同时低甲基化的基因，以及22个下调和伴随高甲基化的基因在HEK 293 T细胞中对AgNPs有反应。值得注意的是，这些基因主要参与脂质代谢和离子代谢。总之，这些响应基因可以通过改变DNA甲基化指纹作为早期表观遗传完整性变化的早期敏感指标，反映银纳米颗粒在实际暴露情况下的生物风险和毒性。
With the rapid development of nanotechnology and nanoscience, nanosafety assessment has raised public concern. Although many studies have illustrated that nanomaterials could lead to genotoxicity, the early alterations of DNA methylation with nanomaterials under low-dose exposure have not been completely clear. In this study, we investigated the potential effect and molecular mechanism of AgNPs on the alternation of DNA methylation fingerprints in HEK293T cells under sublethal exposure. Intriguingly, silver nanoparticle treatment increased 5-mC level and changed methylation-related enzyme contents. Mechanistically, we scrutinized the changes in the molecular signaling and biological functions by means of MeDIP-Seq and RNA-seq. Our results revealed that AgNPs might undermine a number of vital regulatory networks including the metabolic processes, biological regulation and other cellular processes. More specifically at the DNA methylation fingerprints, there were 12 up-regulated and simultaneous hypomethylated genes, and 22 down-regulated and concomitant hypermethylated genes in HEK293T cells responding to AgNPs. Notably, these genes were primarily involved in lipid metabolism and ion metabolism. Together, these responsive genes might be used as early sensitive indicators for the variations of early epigenetic integrity through changing the DNA methylation fingerprints, as reflective of biological risk and toxicity of silver nanoparticles under realistic exposure scenarios.
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