Shenzhen Key Laboratory of Molecular Epidemiology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China.
Shenzhen Key Laboratory of Molecular Epidemiology, Shenzhen Center for Disease Control and Prevention, Shenzhen, China; School of Public Health, Fujian Medical University, Fuzhou, China.
Ecotoxicol Environ Saf. 2019 Jul 30;176:1-10. doi: 10.1016/j.ecoenv.2019.03.055. Epub 2019 Mar 21.
Wide use of titanium dioxide nanoparticles (TiO NPs) as white pigments induces unintentionally release in environment which increases concerns about their adverse health effects on respiratory system. So it is crucial to get a deep understanding of the disease process and molecular mechanism. Epigenetic mechanisms, such as DNA methylation, have been found to play a role in the development of lung diseases by affecting expression of key genes. In addition, there could be potential different toxic effects of TiO NPs between young and adult. Thus, the comparative toxicity of TiO NPs in 5-week (young) and 10-week (adult) old NIH mice is investigated in this study following nasal inhalation of TiO NPs at dose of 20 mg/kg (body weight)/day for 30 days. Global DNA methylation and hydroxymethylation in lung were measured. Promoter methylation of inflammatory genes (IFN-γ and TNF-α) and tissue fibrosis gene (Thy-1) were determined. Additional, RNA-sequencing runs were performed on the pulmonic libraries. We found the induced pulmonary inflammation and fibrosis were more severe in young mice. Decreased global methylation and hydroxymethylation were only found in the young group. The altered methylation in promoter of TNF-α and Thy-1 were found to play a role in the inflammatory response and fibration. RNA-sequencing showed that in pathways in cancer expression of 197 genes was up-regulated in the young mice more that in the adult mice. All these results suggested that the young ages are more sensitive to TiO NP exposure and the potential of abnormal DNA methylation might be used as biomarkers of both exposure and disease development.
由于二氧化钛纳米粒子（TiO NPs）作为白色颜料的广泛应用，其在环境中的无意释放引起了人们对其呼吸系统不良健康影响的关注。因此，深入了解疾病过程和分子机制至关重要。表观遗传机制，如 DNA 甲基化，已被发现通过影响关键基因的表达在肺部疾病的发展中发挥作用。此外，TiO NPs 在年轻人和成年人之间可能存在潜在的不同毒性作用。因此，本研究通过鼻腔内吸入 20mg/kg（体重）/天的 TiO NPs，在 5 周（年轻）和 10 周（成年）龄 NIH 小鼠中研究了 TiO NPs 的比较毒性。测量了肺中的全基因组 DNA 甲基化和羟甲基化。测定了炎症基因（IFN-γ和 TNF-α）和组织纤维化基因（Thy-1）的启动子甲基化。此外，在 pulmonic 文库上进行了 RNA-seq 运行。我们发现，年轻小鼠的肺部炎症和纤维化更为严重。仅在年轻组中发现了全基因组甲基化和羟甲基化的降低。TNF-α和 Thy-1 启动子中改变的甲基化被认为在炎症反应和纤维化中发挥作用。RNA-seq 显示，在癌症途径中，197 个基因的表达在年轻小鼠中比成年小鼠上调更多。所有这些结果表明，年轻时期对 TiO NP 暴露更为敏感，异常 DNA 甲基化的可能性可用作暴露和疾病发展的生物标志物。
