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.
Int J Mol Sci. 2020 Mar 31;21(7):2420. doi: 10.3390/ijms21072420.
The risk of exposure to nanoparticles (NPs) has rapidly increased during the last decade due to the vast use of nanomaterials (NMs) in many areas of human life. Despite this fact, human biomonitoring studies focused on the effect of NP exposure on DNA alterations are still rare. Furthermore, there are virtually no epigenetic data available. In this study, we investigated global and gene-specific DNA methylation profiles in a group of 20 long-term (mean 14.5 years) exposed, nanocomposite, research workers and in 20 controls. Both groups were sampled twice/day (pre-shift and post-shift) in September 2018. We applied Infinium Methylation Assay, using the Infinium MethylationEPIC BeadChips with more than 850,000 CpG loci, for identification of the DNA methylation pattern in the studied groups. Aerosol exposure monitoring, including two nanosized fractions, was also performed as proof of acute NP exposure. The obtained array data showed significant differences in methylation between the exposed and control groups related to long-term exposure, specifically 341 CpG loci were hypomethylated and 364 hypermethylated. The most significant CpG differences were mainly detected in genes involved in lipid metabolism, the immune system, lung functions, signaling pathways, cancer development and xenobiotic detoxification. In contrast, short-term acute NP exposure was not accompanied by DNA methylation changes. In summary, long-term (years) exposure to NP is associated with DNA epigenetic alterations.
在过去的十年中,由于纳米材料(NMs)在人类生活的许多领域中的广泛应用,纳米颗粒(NPs)暴露的风险迅速增加。尽管如此,专注于 NP 暴露对 DNA 改变影响的人体生物监测研究仍然很少。此外,实际上没有可用的表观遗传数据。在这项研究中,我们研究了一组 20 名长期(平均 14.5 年)暴露于纳米复合材料的研究人员和 20 名对照者的全基因组和基因特异性 DNA 甲基化谱。两组人员均于 2018 年 9 月每天两次(班前和班后)进行采样。我们应用 Infinium Methylation Assay,使用 Infinium MethylationEPIC BeadChips 进行检测,该芯片包含超过 850,000 个 CpG 位点,用于鉴定研究组中的 DNA 甲基化模式。还进行了气溶胶暴露监测,包括两个纳米级分数,以证明急性 NP 暴露。获得的阵列数据显示,暴露组和对照组之间存在与长期暴露相关的甲基化差异,具体来说,有 341 个 CpG 位点呈低甲基化,364 个呈高甲基化。最显著的 CpG 差异主要在涉及脂质代谢、免疫系统、肺功能、信号通路、癌症发展和外源性毒物解毒的基因中检测到。相比之下,短期急性 NP 暴露不会导致 DNA 甲基化变化。总之,长期(数年)暴露于 NP 与 DNA 表观遗传改变有关。