探索短期暴露于非功能化聚乙烯纳米颗粒对人类免疫细胞中选定的染色质决定因素和等离子体DNA完整性的影响
Kinga Malinowska1, Kateryna Tarhonska2, Karolina Górecka3,4
1Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
Nanotoxicology
|September 10, 2025
概括
非功能化聚烯纳米颗粒 (PS-NP) 并没有直接破坏DNA. 然而,PS-NPs改变了基因表达和减少了基因子修饰,这表明对染色质结构的潜在表观遗传影响.
科学领域:
- 环境纳米粒子毒理学
- 表观遗传学和基因调控
- 细胞对纳米材料的反应
背景情况:
- 纳米粒子 (NP) 越来越普遍,需要了解它们的生物相互作用.
- 聚乙烯纳米粒子 (PS-NPs) 是常见的,但它们对细胞表观遗传机制的影响仍在研究中.
- 染色体结构在基因表达调节中起着至关重要的作用.
研究的目的:
- 研究非功能化PS-NP对DNA完整性和与染色体结构相关的基因表达的影响.
- 评估不同PS-NP大小 (29,44,72 nm) 和度对人类外周血液单核细胞 (PBMC) 的影响.
- 检查DNA甲基化,脱甲基化,基因素修饰和乙化标记物的变化.
主要方法:
- 在24小时内,在度范围 (0.001100μg/mL) 中,将人类PBMC与PS-NP (29,44,72 nm) 进行化.
- 对参与DNA甲基化 (DNMT1,DNMT3A),脱甲基化 (TET2,TET3) 和染色质重塑 (EHMT1,EHMT2,HDAC3,HDAC5) 的基因进行定量实时PCR.
- 对于表观遗传标记 (H3ac,H3K4me3,H3K9me3) 和DNA完整性的等离子体放松试验,西方涂抹.
主要成果:
- 在细胞外等离子体放松试验中,PS-NP没有表现出直接的DNA裂变活性.
- 大多数研究的基因 (DNMT1,TET2,TET3,EHMT1,EHMT2,HDAC3,HDAC5) 的表达没有明显的变化.
- 在29nm的PS-NP中发现了DNMT3A基因表达的统计学显著变化,并且观察到H3ac和H3K4me3蛋白水平的显著下降.
结论:
- 非功能化的PS-NP不会直接损害等离子体DNA.
- 通过降低特定的质子修饰 (H3ac,H3K4me3) ,PS-NP可能会影响表观遗传调节.
- 这些发现表明PS-NPs可能会通过表观遗传途径影响染色体结构调节.
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