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Differential genotoxicity mechanisms of silver nanoparticles and silver ions.
Arch Toxicol. 2017 Jan; 91(1):509-519.AT

Abstract

In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. A key question is whether the observed toxicity comes from the silver ions (Ag+) released from the AgNPs or from the nanoparticles themselves. In this study, we explored the genotoxicity and the genotoxicity mechanisms of Ag+ and AgNPs. Human TK6 cells were treated with 5 nM AgNPs or silver nitrate (AgNO3) to evaluate their genotoxicity and induction of oxidative stress. AgNPs and AgNO3 induced cytotoxicity and genotoxicity in a similar range of concentrations (1.00-1.75 µg/ml) when evaluated using the micronucleus assay, and both induced oxidative stress by measuring the gene expression and reactive oxygen species in the treated cells. Addition of N-acetylcysteine (NAC, an Ag+ chelator) to the treatments significantly decreased genotoxicity of Ag+, but not AgNPs, while addition of Trolox (a free radical scavenger) to the treatment efficiently decreased the genotoxicity of both agents. In addition, the Ag+ released from the highest concentration of AgNPs used for the treatment was measured. Only 0.5 % of the AgNPs were ionized in the culture medium and the released silver ions were neither cytotoxic nor genotoxic at this concentration. Further analysis using electron spin resonance demonstrated that AgNPs produced hydroxyl radicals directly, while AgNO3 did not. These results indicated that although both AgNPs and Ag+ can cause genotoxicity via oxidative stress, the mechanisms are different, and the nanoparticles, but not the released ions, mainly contribute to the genotoxicity of AgNPs.

Authors+Show Affiliations

Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR, USA. Covance Laboratories Inc., 671 South Meridian Rd, Greenfield, IN, 46140, USA.Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR, USA. Bio-Medical Pharmaceutical Manufacturing Corporation, 4311 South Drive, Houston, TX, 77053, USA.Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA.Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR, USA.Division of Analytical Chemistry, Office of Regulatory Science, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, MD, USA. Key Laboratory of Micro-Nano Materials for Energy Storage and Conversion of Henan Province, Institute of Surface Micro and Nano Materials, Kuching University, Henan, 461000, People's Republic of China.Division of Analytical Chemistry, Office of Regulatory Science, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, College Park, MD, USA.Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR, USA. tao.chen@fda.hhs.gov.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

27180073

Citation

Li, Yan, et al. "Differential Genotoxicity Mechanisms of Silver Nanoparticles and Silver Ions." Archives of Toxicology, vol. 91, no. 1, 2017, pp. 509-519.
Li Y, Qin T, Ingle T, et al. Differential genotoxicity mechanisms of silver nanoparticles and silver ions. Arch Toxicol. 2017;91(1):509-519.
Li, Y., Qin, T., Ingle, T., Yan, J., He, W., Yin, J. J., & Chen, T. (2017). Differential genotoxicity mechanisms of silver nanoparticles and silver ions. Archives of Toxicology, 91(1), 509-519. https://doi.org/10.1007/s00204-016-1730-y
Li Y, et al. Differential Genotoxicity Mechanisms of Silver Nanoparticles and Silver Ions. Arch Toxicol. 2017;91(1):509-519. PubMed PMID: 27180073.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential genotoxicity mechanisms of silver nanoparticles and silver ions. AU - Li,Yan, AU - Qin,Taichun, AU - Ingle,Taylor, AU - Yan,Jian, AU - He,Weiwei, AU - Yin,Jun-Jie, AU - Chen,Tao, Y1 - 2016/05/14/ PY - 2015/10/16/received PY - 2016/04/27/accepted PY - 2016/5/18/pubmed PY - 2017/3/8/medline PY - 2016/5/16/entrez KW - Cytotoxicity KW - Genotoxicity KW - In vitro micronucleus assay KW - Oxidative stress KW - Silver ion KW - Silver nanoparticles SP - 509 EP - 519 JF - Archives of toxicology JO - Arch Toxicol VL - 91 IS - 1 N2 - In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. A key question is whether the observed toxicity comes from the silver ions (Ag+) released from the AgNPs or from the nanoparticles themselves. In this study, we explored the genotoxicity and the genotoxicity mechanisms of Ag+ and AgNPs. Human TK6 cells were treated with 5 nM AgNPs or silver nitrate (AgNO3) to evaluate their genotoxicity and induction of oxidative stress. AgNPs and AgNO3 induced cytotoxicity and genotoxicity in a similar range of concentrations (1.00-1.75 µg/ml) when evaluated using the micronucleus assay, and both induced oxidative stress by measuring the gene expression and reactive oxygen species in the treated cells. Addition of N-acetylcysteine (NAC, an Ag+ chelator) to the treatments significantly decreased genotoxicity of Ag+, but not AgNPs, while addition of Trolox (a free radical scavenger) to the treatment efficiently decreased the genotoxicity of both agents. In addition, the Ag+ released from the highest concentration of AgNPs used for the treatment was measured. Only 0.5 % of the AgNPs were ionized in the culture medium and the released silver ions were neither cytotoxic nor genotoxic at this concentration. Further analysis using electron spin resonance demonstrated that AgNPs produced hydroxyl radicals directly, while AgNO3 did not. These results indicated that although both AgNPs and Ag+ can cause genotoxicity via oxidative stress, the mechanisms are different, and the nanoparticles, but not the released ions, mainly contribute to the genotoxicity of AgNPs. SN - 1432-0738 UR - https://www.unboundmedicine.com/medline/citation/27180073/Differential_genotoxicity_mechanisms_of_silver_nanoparticles_and_silver_ions_ DB - PRIME DP - Unbound Medicine ER -