Multi-locus deletion mutation induced by silver nanoparticles: Role of lysosomal-autophagy dysfunction

Bo Si; Xue Wang; Yun Liu; Juan Wang; Yemian Zhou; Yaguang Nie; An Xu

doi:10.1016/j.ecoenv.2023.114947

Multi-locus deletion mutation induced by silver nanoparticles: Role of lysosomal-autophagy dysfunction

Ecotoxicol Environ Saf. 2023 Jun 1:257:114947. doi: 10.1016/j.ecoenv.2023.114947. Epub 2023 Apr 25.

Authors

Bo Si¹, Xue Wang², Yun Liu³, Juan Wang⁴, Yemian Zhou³, Yaguang Nie⁵, An Xu⁶

Affiliations

¹ 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.
² School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, PR China.
³ 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.
⁴ Department of Public Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, Anhui 230032, PR China.
⁵ Information Materials and Intelligent Sensing Laboratory of Anhui Province, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui 230601, PR China. Electronic address: nyg@ahu.edu.cn.
⁶ 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. Electronic address: anxu@ipp.ac.cn.

PMID: 37105094
DOI: 10.1016/j.ecoenv.2023.114947

Abstract

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 (A_L) 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.

Keywords: Autophagy dysfunction; Genotoxicity; Lysosomal impairment; Multi-locus deletion mutation; Silver nanoparticles (AgNPs).

MeSH terms

Animals
Autophagy / genetics
Humans
Lysosomes
Mammals
Metal Nanoparticles* / toxicity
Sequence Deletion
Silver* / toxicity

Substances

Silver