RRC ID 55914
著者 Horie M, Shimizu K, Tabei Y.
タイトル Validation of metallothionein, interleukin-8, and heme oxygenase-1 as markers for the evaluation of cytotoxicity caused by metal oxide nanoparticles.
ジャーナル Toxicol Mech Methods
Abstract Metal oxide nanoparticles have an industrial value, although their harmful effects are also known. Induction of respiratory inflammation through their inhalation is a serious indicator of their toxicity. Although the phenomenon of metal ion release is involved in the induction of inflammation, all metal ions are not necessarily toxic. However, currently, no particular index to evaluate cytotoxicity caused by nanoparticles exists. An index based on biological response is critical. In the present study, we examined the gene expression-based index for nanoparticle-derived cytotoxicity. The cellular effects of six kinds of metal oxide nanoparticles, ZnO, NiO, CuO, MgO, Bi2O3, and MoO3 on A549 cells were examined. It was seen that lactate dehydrogenase (LDH) assay, which is one of the most important assays for assessing cell membrane damage, is inhibited by metal ions released from the metal oxide nanoparticles. In some cases, enzyme activity-based assay was not suitable for the evaluation of cytotoxicity of nanoparticles. ZnO and CuO nanoparticles displayed severe cytotoxicity and enhanced gene expression of heme oxygenase-1 (HO-1) and interleukin-8 (IL-8). The IL-8 gene expression was also increased from Bi2O3 exposure. Additionally, the gene expression of metallothionein 2A (MT2A) was enhanced in the ZnO, CuO, and Bi2O3 exposed cells. These results suggest that these nanoparticles released metal ions in the cells. The enhancement of HO-1, IL-8, and MT2A gene expressions was related to the cytotoxic activity of metal oxide nanoparticles. Thus, the expression level of these genes is a good indicator of nanotoxicology of metal oxide nanoparticles.
巻・号 28(8)
ページ 630-638
公開日 2018-10-1
DOI 10.1080/15376516.2018.1486931
PMID 29882686
MeSH A549 Cells Biomarkers / metabolism Cell Membrane / drug effects Cell Membrane / metabolism Cell Survival / drug effects Dose-Response Relationship, Drug Gene Expression / drug effects Heme Oxygenase-1 / metabolism* Humans Interleukin-8 / metabolism* Metal Nanoparticles / chemistry Metal Nanoparticles / toxicity* Metallothionein / genetics Metallothionein / metabolism* Oxidative Stress / drug effects* Oxidative Stress / genetics Oxides
IF 1.994
引用数 2
リソース情報
ヒト・動物細胞 A549