Wang Xue, Nie Yaguang, Si Bo, Wang Tong, Hei Tom K, Du Hua, Zhao Guoping, Chen Shaopeng, Xu An, Liu Yun
School of Environmental Science and Optoelectronic Technology, University of Science and Technology of China, Hefei, Anhui 230026, PR China; Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Chinese Academy of Sciences; Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology, High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, PR China.
Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, PR China.
J Hazard Mater. 2021 Jul 5;413:125287. doi: 10.1016/j.jhazmat.2021.125287. Epub 2021 Feb 5.
Arsenic (As) and its compounds have been classified as Group I carcinogenic agents by the International Agency for Research on Cancer (IARC); however, there is few specific and efficient antidotes used for As detoxification. The present study aimed to investigate the protective effects of silver nanoparticles (AgNPs) at non-toxic concentrations on As(Ⅲ) induced genotoxicity and the underlying mechanism. Our data showed that AgNPs pretreatment significantly inhibited the generation of phosphorylated histone H2AX (γ-H2AX, marker of nuclear DNA double strand breaks) and the mutation frequencies induced by As(Ⅲ) exposure. Atomic fluorescence spectrometer (AFS) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) analysis revealed that the intracellular accumulation of As(Ⅲ) in human-hamster hybrid A cells was declined by AgNPs via suppressing the expression of specific As(Ⅲ)-binding protein (Gal-1). Moreover, the activities of antioxidant enzymes were greatly up-regulated by AgNPs, which eventually inhibited the generation of reactive oxygen species (ROS) induced by As(Ⅲ) and the downstream stress-activated protein kinases/c-Jun amino-terminal kinases (SAPK/JNK) signaling pathway. These results provided clear evidence that AgNPs dramatically suppressed the genotoxic response of As(Ⅲ) in mammalian cells via decreasing As(Ⅲ) bioaccumulation and elevating intracellular antioxidation, which might provide a new clue for AgNPs applications in As(Ⅲ) detoxification.
砷（As）及其化合物已被国际癌症研究机构（IARC）列为I类致癌物质；然而，用于砷解毒的特异性高效解毒剂却很少。本研究旨在探讨无毒浓度的银纳米颗粒（AgNPs）对As（Ⅲ）诱导的遗传毒性的保护作用及其潜在机制。我们的数据表明，AgNPs预处理显著抑制了磷酸化组蛋白H2AX（γ-H2AX，核DNA双链断裂的标志物）的产生以及As（Ⅲ）暴露诱导的突变频率。原子荧光光谱仪（AFS）和激光烧蚀-电感耦合等离子体质谱仪（LA-ICP-MS）分析表明，AgNPs通过抑制特异性As（Ⅲ）结合蛋白（Gal-1）的表达，降低了人-仓鼠杂交A细胞中As（Ⅲ）的细胞内积累。此外，AgNPs极大地上调了抗氧化酶活性，并最终抑制了As（Ⅲ）诱导的活性氧（ROS）的产生以及下游应激激活蛋白激酶/c-Jun氨基末端激酶（SAPK/JNK）信号通路。这些结果提供了明确的证据，表明AgNPs通过减少As（Ⅲ）生物积累和提高细胞内抗氧化作用，显著抑制了哺乳动物细胞中As（Ⅲ）的遗传毒性反应，这可能为AgNPs在As（Ⅲ）解毒中的应用提供新线索。
