Abstract
BackgroundSubtle DNA methylation alterations mediated by carbon nanotubes (CNTs) exposure might contribute to pathogenesis and disease susceptibility. It is known that both multi-walled carbon nanotubes (MWCNTs) and single-walled carbon nanotubes (SWCNTs) interact with nucleus. Such, nuclear-CNT interaction may affect the DNA methylation effects.In order to understand the epigenetic toxicity, in particular DNA methylation alterations, of SWCNTs and short MWCNTs, we performed global/genome-wide, gene-specific DNA methylation and RNA-expression analyses after exposing human bronchial epithelial cells (16HBE14o- cell line). In addition, the presence of CNTs on/in the cell nucleus was evaluated in a label-free way using femtosecond pulsed laser microscopy.ResultsGenerally, a higher number of SWCNTs, compared to MWCNTs, was deposited at both the cellular and nuclear level after exposure. Nonetheless, both CNT types were in physical contact with the nuclei. While particle type dependency was noticed for the identified genome-wide and gene-specific alterations, no global DNA methylation alteration on 5-methylcytosine (5-mC) sites was observed for both CNTs. After exposure to MWCNTs, 2398 genes were hypomethylated (at gene promoters), and after exposure to SWCNTs, 589 CpG sites (located on 501 genes) were either hypo- (N = 493 CpG sites) or hypermethylated (N = 96 CpG sites).Cells exposed to MWCNTs exhibited a better correlation between gene promoter methylation and gene expression alterations. Differentially methylated and expressed genes induced changes (MWCNTs > SWCNTs) at different cellular pathways, such as p53 signalling, DNA damage repair and cell cycle. On the other hand, SWCNT exposure showed hypermethylation on functionally important genes, such as SKI proto-oncogene (SKI), glutathione S-transferase pi 1 (GTSP1) and shroom family member 2 (SHROOM2) and neurofibromatosis type I (NF1), which the latter is both hypermethylated and downregulated.ConclusionAfter exposure to both types of CNTs, epigenetic alterations may contribute to toxic or repair response. Moreover, our results suggest that the observed differences in the epigenetic response depend on particle type and differential CNT-nucleus interactions.
Highlights
Subtle DNA methylation alterations mediated by carbon nanotubes (CNTs) exposure might contribute to pathogenesis and disease susceptibility
Characterisation of Cnts multi-walled carbon nanotubes (MWCNTs) and single-walled carbon nanotubes (SWCNTs) were obtained from the European Commission Joint Research Centre (JRC, Ispra, Italy) and the National Institute of Technology (NIST, Gaithersburg, Maryland, USA), respectively
Our analysis shows that SWCNTs have significantly more physical contact with nuclei compared to MWCNTs
Summary
Subtle DNA methylation alterations mediated by carbon nanotubes (CNTs) exposure might contribute to pathogenesis and disease susceptibility. It is known that both multi-walled carbon nanotubes (MWCNTs) and single-walled carbon nanotubes (SWCNTs) interact with nucleus. Carbon nanotubes (CNTs) are a class of graphene-based engineered nanomaterials. These have a tubular and fibre structure with a diameter in nanometer (nm). CNTs can be divided into categories by the number of layers of the rolled-up graphene, which will define their diameter size: e.g. single-walled CNTs (SWCNTs) with a diameter between 0.7 and 3 nm and multi-walled CNTs (MWCNTs) with a diameter between 10 and 200 nm [1]. SWCNTs are present in stiff, rope-like bundles due to the increased van der Waals forces caused by their extremely small diameter and high surface area. The market of CNTs is expected to keep on growing in the five years based on several online market reports
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