Comparative genotoxicity of silver nanoparticles in human liver HepG2 and lung epithelial A549 cells

Autor: Qiulin Luo, Lili Xin, Guangzhu Dong, Bizhong Che, Leshuai W. Zhang, Jianshu Wang
Rok vydání: 2016
Předmět:
Zdroj: Journal of Applied Toxicology. 37:495-501
ISSN: 0260-437X
DOI: 10.1002/jat.3385
Popis: With the rapid expanding of human exposure to silver nanoparticles (AgNPs), genotoxicity screening of nanosilver is necessary to ensure consumer safety. Here, we assessed one key DNA damage responsive pathway activated by GADD45a gene after 24 h of AgNPs exposure in stable luciferase reporter cell systems based on two widely used in vitro cell models, human liver HepG2 and lung epithelial A549 cells. The comet assay and micronucleus test were also conducted to confirm the genetic damage induced by AgNPs. Our results showed that AgNPs produced a strong dose-dependent increase in transcriptional activation of GADD45a promoter indicated by luciferase activity accompanying by the significant decreases in cell viability. Surprisingly, in HepG2-luciferase cells, the relative luciferase activity was greater than 4.5× the control level after being treated with 200 μg ml-1 AgNPs. These results were generally in line with the positive and dose-dependent responses in cytotoxicity, DNA strand breaks indicated by Olive tail moment, tail DNA (%) and tail length, and chromosome damage indicated by induction of micronuclei, nucleoplasmic bridges, and nuclear buds. Additionally, compared with the A549-luciferase cells, the HepG2-luciferase cells seemed to be more susceptible to AgNPs as higher levels of genotoxicity were induced. We concluded that our GADD45a promoter-driven luciferase reporter gene cell system, together with the comet assay and micronucleus test, can be used as valuable tools for rapid screening of genotoxic potential of nanosilver. Copyright © 2016 John Wiley & Sons, Ltd.
Databáze: OpenAIRE