Seidel Carole, Kirsch Anaïs, Fontana Caroline, Visvikis Athanase, Remy Aurélie, Gaté Laurent, Darne Christian, Guichard Yves
a Département Toxicologie et Biométrologie , Institut National de Recherche et Sécurité (INRS) , Vandoeuvre-lès-Nancy Cedex , France.
b Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA) , UMR 7365 CNRS-Université de Lorraine, Biopôle, Campus Biologie Santé , Vandoeuvre-lès-Nancy , France.
Nanotoxicology. 2017 Sep;11(7):923-935. doi: 10.1080/17435390.2017.1382599. Epub 2017 Sep 28.
The increasing use of nanomaterials in numerous domains has led to growing concern about their potential toxicological properties, and the potential risk to human health posed by silica nanoparticles remains under debate. Recent studies proposed that these particles could alter gene expression through the modulation of epigenetic marks, and the possible relationship between particle exposure and these mechanisms could represent a critical factor in carcinogenicity. In this study, using the Bhas 42 cell model, we compare the effects of exposure to two transforming particles, a pyrogenic amorphous silica nanoparticle NM-203 to those of the crystalline silica particle Min-U-Sil 5. Short-term treatment by Min-U-Sil 5 decreased global DNA methylation and increased the expression of the two de novo DNMTs, DNMT3a and DNMT3b. NM-203 treatment affected neither the expression of these enzymes nor DNA methylation. Moreover, modified global histone H4 acetylation status and HDAC protein levels were observed only in the Min-U-Sil 5-treated cells. Finally, both types of particle treatment induced strong c-Myc expression in the early stage of cell transformation and this correlated with enrichment in RNA polymerase II as well as histone active marks on its promoter. Lastly, almost all parameters that were modulated in the early stage were restored in transformed cells suggesting their involvement mainly in the first steps of cell transformation.
纳米材料在众多领域的使用日益增加，引发了人们对其潜在毒理学特性的日益关注，而二氧化硅纳米颗粒对人类健康构成的潜在风险仍存在争议。最近的研究表明，这些颗粒可能通过调节表观遗传标记来改变基因表达，颗粒暴露与这些机制之间的可能关系可能是致癌性的关键因素。在本研究中，我们使用Bhas 42细胞模型，比较了暴露于两种转化颗粒——热解无定形二氧化硅纳米颗粒NM - 203和结晶二氧化硅颗粒Min - U - Sil 5的影响。Min - U - Sil 5的短期处理降低了整体DNA甲基化，并增加了两种从头DNMT（DNA甲基转移酶），即DNMT3a和DNMT3b的表达。NM - 203处理既不影响这些酶的表达，也不影响DNA甲基化。此外，仅在Min - U - Sil 5处理的细胞中观察到修饰的整体组蛋白H4乙酰化状态和HDAC（组蛋白去乙酰化酶）蛋白水平。最后，两种类型的颗粒处理在细胞转化早期均诱导了强烈的c - Myc表达，这与RNA聚合酶II以及其启动子上的组蛋白活性标记的富集相关。最后，几乎所有在早期被调节的参数在转化细胞中都恢复了，这表明它们主要参与细胞转化的第一步。
