Multi-locus deletion mutation induced by silver nanoparticles: Role of lysosomal-autophagy dysfunction
Due to the rapid production growth and a wide range of applications, safety concerns are being raised about the genotoxic properties of silver nanoparticles (AgNPs). In this research, we found AgNPs induced a size-dependent genotoxicity via lysosomal-autophagy dysfunction in human-hamster hybrid (AL...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323004517 |
| _version_ | 1797833144030724096 |
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| author | Bo Si Xue Wang Yun Liu Juan Wang Yemian Zhou Yaguang Nie An Xu |
| author_facet | Bo Si Xue Wang Yun Liu Juan Wang Yemian Zhou Yaguang Nie An Xu |
| author_sort | Bo Si |
| collection | DOAJ |
| description | Due to the rapid production growth and a wide range of applications, safety concerns are being raised about the genotoxic properties of silver nanoparticles (AgNPs). In this research, we found AgNPs induced a size-dependent genotoxicity via lysosomal-autophagy dysfunction in human-hamster hybrid (AL) cells. Compared with 25 nm and 75 nm particles, 5 nm AgNPs could accentuate the genotoxic responses, including DNA double-strand breaks (DSBs) and multi-locus deletion mutation, which could be significantly enhanced by autophagy inhibitors 3-methyl adenine (3-MA), Bafilomycin A1 (BFA), and cathepsin inhibitors, respectively. The autophagy dysfunction was closely related to the accumulation of 5 nm AgNPs in the lysosomes and the interruption of lysosome-autophagosome fusion. With lysosomal protective agent 3-O-Methylsphingomyelin (3-O-M) and endocytosis inhibitor wortmannin, the reactivation of lysosomal function and the recovery of autophagy significantly attenuated AgNP-induced genotoxicity. Our data provide clear evidence to illustrate the role of subcellular targets in the genotoxicity of AgNPs in mammalian cells, which laid the basis for better understanding the health risk of AgNPs and their related products. |
| first_indexed | 2024-04-09T14:19:51Z |
| format | Article |
| id | doaj.art-a6768c73e48d499dbeb8054c7cdd9a20 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-09T14:19:51Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-a6768c73e48d499dbeb8054c7cdd9a202023-05-05T04:39:44ZengElsevierEcotoxicology and Environmental Safety0147-65132023-06-01257114947Multi-locus deletion mutation induced by silver nanoparticles: Role of lysosomal-autophagy dysfunctionBo Si0Xue Wang1Yun Liu2Juan Wang3Yemian Zhou4Yaguang Nie5An Xu6Key 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; University of Science and Technology of China, Hefei, Anhui 230026, PR ChinaSchool of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, PR ChinaKey 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 ChinaDepartment of Public Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, Anhui 230032, PR ChinaKey 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 ChinaInformation Materials and Intelligent Sensing Laboratory of Anhui Province, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, PR China; Corresponding author.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; University of Science and Technology of China, Hefei, Anhui 230026, PR China; Information Materials and Intelligent Sensing Laboratory of Anhui Province, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, PR China; Corresponding author at: 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.Due to the rapid production growth and a wide range of applications, safety concerns are being raised about the genotoxic properties of silver nanoparticles (AgNPs). In this research, we found AgNPs induced a size-dependent genotoxicity via lysosomal-autophagy dysfunction in human-hamster hybrid (AL) cells. Compared with 25 nm and 75 nm particles, 5 nm AgNPs could accentuate the genotoxic responses, including DNA double-strand breaks (DSBs) and multi-locus deletion mutation, which could be significantly enhanced by autophagy inhibitors 3-methyl adenine (3-MA), Bafilomycin A1 (BFA), and cathepsin inhibitors, respectively. The autophagy dysfunction was closely related to the accumulation of 5 nm AgNPs in the lysosomes and the interruption of lysosome-autophagosome fusion. With lysosomal protective agent 3-O-Methylsphingomyelin (3-O-M) and endocytosis inhibitor wortmannin, the reactivation of lysosomal function and the recovery of autophagy significantly attenuated AgNP-induced genotoxicity. Our data provide clear evidence to illustrate the role of subcellular targets in the genotoxicity of AgNPs in mammalian cells, which laid the basis for better understanding the health risk of AgNPs and their related products.http://www.sciencedirect.com/science/article/pii/S0147651323004517Silver nanoparticles (AgNPs)GenotoxicityLysosomal impairmentAutophagy dysfunctionMulti-locus deletion mutation |
| spellingShingle | Bo Si Xue Wang Yun Liu Juan Wang Yemian Zhou Yaguang Nie An Xu Multi-locus deletion mutation induced by silver nanoparticles: Role of lysosomal-autophagy dysfunction Ecotoxicology and Environmental Safety Silver nanoparticles (AgNPs) Genotoxicity Lysosomal impairment Autophagy dysfunction Multi-locus deletion mutation |
| title | Multi-locus deletion mutation induced by silver nanoparticles: Role of lysosomal-autophagy dysfunction |
| title_full | Multi-locus deletion mutation induced by silver nanoparticles: Role of lysosomal-autophagy dysfunction |
| title_fullStr | Multi-locus deletion mutation induced by silver nanoparticles: Role of lysosomal-autophagy dysfunction |
| title_full_unstemmed | Multi-locus deletion mutation induced by silver nanoparticles: Role of lysosomal-autophagy dysfunction |
| title_short | Multi-locus deletion mutation induced by silver nanoparticles: Role of lysosomal-autophagy dysfunction |
| title_sort | multi locus deletion mutation induced by silver nanoparticles role of lysosomal autophagy dysfunction |
| topic | Silver nanoparticles (AgNPs) Genotoxicity Lysosomal impairment Autophagy dysfunction Multi-locus deletion mutation |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323004517 |
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