Epigenetic changes in the early stage of silica-induced cell transformation

• Published in: Nanotoxicology Vol. 11; no. 7; pp. 923 - 935
• Main Authors: Seidel, Carole, Kirsch, Anaïs, Fontana, Caroline, Visvikis, Athanase, Remy, Aurélie, Gaté, Laurent, Darne, Christian, Guichard, Yves
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01-09-2017; Taylor & Francis Ltd
• Subjects: Acetylation; c-myc expression; c-Myc protein; Carcinogenicity; Carcinogens; Cell Line; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - genetics; Deoxyribonucleic acid; DNA; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA methylation; DNA Methylation - drug effects; DNA Methyltransferase 3A; DNA Methyltransferase 3B; DNA-directed RNA polymerase; Engineering Sciences; Epigenesis, Genetic - drug effects; epigenetic modifications; Epigenetics; Exposure; Gene expression; Gene Expression - drug effects; Genetic transformation; HDAC protein; Health risks; Histone deacetylase; Histone H4; Histones - genetics; Human health and pathology; Humans; Life Sciences; Micro and nanotechnologies; Microelectronics; Myc protein; Nanomaterials; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - toxicity; Nanotechnology; Particulates; Promoter Regions, Genetic; Promotion assay; Proto-Oncogene Proteins c-myc - genetics; Ribonucleic acid; RNA; RNA polymerase II; Silica; silica particles; Silicon dioxide; Silicon Dioxide - chemistry; Silicon Dioxide - toxicity; Surface Properties; Toxicology; Transformed cells; silica particles; epigenetic modifications; Promotion assay; c-myc expression; CYTOTOXICITE; ETAT AMORPHE; GENOTOXICITE; C-myc expression; Silica particles; PRODUIT CHIMIQUE; CANCEROGENICITE; ETAT CRISTALLIN; RECHERCHE; Epigenetic modifications; EXPERIMENTATION; SILICE
• ISSN: 1743-5390; 1743-5404
• DOI: 10.1080/17435390.2017.1382599

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.