Abstract
The toxic effects of silica nanoparticles (SiNPs) are raising concerns due to its widely applications in biomedicine. However, current information about the epigenetic toxicity of SiNPs is insufficient. In this study, the epigenetic regulation of low-dose exposure to SiNPs was evaluated in human bronchial epithelial BEAS-2B cells over 30 passages. Cell viability was decreased in a dose- and passage-dependent manner. The apoptotic rate, the expression of caspase-9 and caspase-3, were significantly increased induced by SiNPs. HumanMethylation450 BeadChip analysis identified that the PI3K/Akt as the primary apoptosis-related pathway among the 25 significant altered processes. The differentially methylated sites of PI3K/Akt pathway involved 32 differential genes promoters, in which the CREB3L1 and Bcl-2 were significant hypermethylated. The methyltransferase inhibitor, 5-aza, further verified that the DNA hypermethylation status of CREB3L1 and Bcl-2 were associated with downregulation of their mRNA levels. In addition, mitochondrial-mediated apoptosis was triggered by SiNPs via the downregulation of PI3K/Akt/CREB/Bcl-2 signaling pathway. Our findings suggest that long-term low-dose exposure to SiNPs could lead to epigenetic alterations.
Highlights
The nanotechnology industry has grown exponentially over the last decade in a diverse range of applications, including medicine, food ingredients, cosmetics, and electronics [1,2]
Our results demonstrated that the DNA hypermethylation status of CREB3L1 and Bcl-2 decreased their mRNA levels of SiNPs-treated BEAS-2B cells
The present study demonstrated that low-dose exposure of SiNPs induced cytotoxicity and mitochondrial-mediated apoptosis in a passage-dependent manner in BEAS-2B cells
Summary
The nanotechnology industry has grown exponentially over the last decade in a diverse range of applications, including medicine (therapeutic, diagnostic and bio-imaging), food ingredients, cosmetics, and electronics [1,2]. More than 1600 consumer products containing nanomaterials are currently available in our daily life [3]. According to reports in the Project on Emerging Nanotechnologies, silica nanoparticles (SiNPs) are listed within the Top 3 nanomaterials-based consumer products [4]. With the growing number of applications for SiNPs, the potential burden on human and environmental exposure are increasing. Humans can be PLOS ONE | DOI:10.1371/journal.pone.0158475. Humans can be PLOS ONE | DOI:10.1371/journal.pone.0158475 June 30, 2016
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