Abstract
Nano silicon dioxide (Nano-SiO2) has been widely used in industries such as the field of biomedical engineering. Despite the existing evidence that Nano-SiO2 exposure could induce oxidative stress and inflammatory responses in multiple organ systems, the carcinogenicity of Nano-SiO2 exposure has rarely been investigated. Thus in this study, two types of human bronchial epithelial cell lines (16HBE and BEAS-2B) were selected as in vitro models to investigate the carcinogenicity of Nano-SiO2. Our results revealed that Nano-SiO2 induces a malignant cellular transformation in human bronchial epithelial cells according to the soft agar colony formation assay. The carcinogenesis induced by Nano-SiO2 was also confirmed in nude mice. By using immunofluorescence assay and high-performance capillary electrophoresis (HPCE), we observed a genome-wide DNA hypomethylation induced by Nano-SiO2. Besides the reduced enzyme activity of total DNMTs upon Nano-SiO2 treatment, altered expression of DNMTs and methyl-CpG binding proteins were observed. Besides, we found that the expression of NRF2 was activated by demethylation of CpG islands within the NRF2 promoter region and the overexpression of NRF2 could alleviate the carcinogenesis induced by Nano-SiO2. Taken together, our results suggested that Nano-SiO2 induces malignant cellular transformation with a global DNA hypomethylation, and the demethylation of NRF2 promoter activates the expression of NRF2, which plays an important role in protecting against the carcinogenesis induced by Nano-SiO2.
Highlights
Nano silicon dioxide (Silica nanoparticles, Nano-SiO2), due to its special characteristics of large surface area and optical transparency, has been widely used in various fields including biomedical imaging, drug delivery, cosmetics, and electronics industry (Vivero-Escoto et al, 2012; Sweeney et al, 2016; Mohajerani et al, 2019)
Since the respiratory system is the primary site that exposed to the airborne Nano-SiO2 particles (Song et al, 2009; Yu et al, 2015), two types of human bronchial epithelial cell lines (16HBE and BEAS-2B) were selected as our in vitro models
We further investigated the expression of Nuclear factor erythroid-2-related factor 2 (NRF2) gene using Quantitative Reverse Transcription-PCR (qRT-PCR) for mRNA and western blot analysis for protein in cells treated with Nano-SiO2
Summary
Nano silicon dioxide (Silica nanoparticles, Nano-SiO2), due to its special characteristics of large surface area and optical transparency, has been widely used in various fields including biomedical imaging, drug delivery, cosmetics, and electronics industry (Vivero-Escoto et al, 2012; Sweeney et al, 2016; Mohajerani et al, 2019). Its widespread applications raise potential health risks to humans through occupational and environmental exposure. Long-lasting nanomaterials in certain tissues have been reported to cause chronic adverse effects such as carcinogenesis due to their special physicochemical properties (Hirose et al, 2011), and nano-sized particles might be more carcinogenic than micron-sized particles concerning long-term exposure (Gebel, 2012). Inhalation of TiO2 nanoparticles was shown to increase the risk of lung cancers in rats (Bermudez et al, 2004) and carbon nanotube exposure through inhalation is carcinogenic to the lungs of male and female rats (Kasai et al, 2016). SiO2 has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) in 1997 (Iarc., 1997), there is limited data on carcinogenicity following chronic exposure to Nano-SiO2. Nano-SiO2 can be localized to the nucleus thereby affecting nuclear integrity and causing DNA damage (Chen and von Mikecz, 2005; Wang et al, 2007)
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