ヨゴサワ　シンゴ   YOGOSAWA Shingo   与五沢　真吾    所属   埼玉医科大学  保健医療学部 臨床検査学科    職種   准教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読あり
表題	Potential role of mitochondrial damage and S9 mixture including metabolic enzymes in ZnO nanoparticles-induced oxidative stress and genotoxicity in Chinese hamster lung (CHL/IU) cells.
掲載誌名	正式名：Mutation research. Genetic toxicology and environmental mutagenesis ISSNコード：0027-5107
掲載区分	国外
巻・号・頁	834,25-34頁
著者・共著者	Hiroyuki Yanagisawa,Yoshiko Seki,Shingo Yogosawa,Shota Takumi,Hidesuke Shimizu,Machi Suka
発行年月	2018/10
概要	The present study was designed to examine genotoxicity induced by 10-40 nm zinc oxide (ZnO) nanoparticles using the in vitro system. The frequency of micronuclei was significantly increased in a dose-dependent manner when cultured Chinese hamster lung (CHL/IU) cells were exposed to ZnO nanoparticles for 24, 48 and 72 h in the continuous treatment method. The maximal frequency of micronuclei was observed in exposure of CHL/IU cells to ZnO nanoparticles at a concentration of 125 μM. The frequency of micronuclei was profoundly enhanced when CHL/IU cells were exposed to ZnO nanoparticles in the presence vs. absence of S9 mixture including metabolic enzymes in the short-term treatment method, demonstrating an increase in the formation of micronuclei by S9 mixture. The maximal frequency of micronuclei was seen in exposure of CHL/IU cells to ZnO nanoparticles at a concentration of 140 μM. Similar results were obtained in chromosome aberrations, particularly structural aberrations. Surprisingly, administration of the superoxide radical scavenger, tempol, completely abolished an increase in the frequency of micronuclei in the presence or absence of S9 mixture, indicating a central role of superoxide radical in the formation of micronuclei. Indeed, reactive oxygen species (ROS) generation was elevated by simultaneous incubation of S9 mixture and ZnO nanoparticles and by exposure of CHL/IU cells to ZnO nanoparticles in the presence or absence of S9 mixture. An electron microscopic examination revealed mitochondrial damage in CHL/IU cells exposed to ZnO nanoparticles, indicating the participation of mitochondrial dysfunction in ROS generation in this setting. These observations suggest that ZnO nanoparticles evoke genotoxicity through superoxide radical-induced oxidative stress derived from mitochondrial damage in CHL/IU cells. S9 mixture appears to contribute to a further increase in genotoxicity through the generation of superoxide radical by metabolic activation of ZnO nanoparticles.
DOI	10.1016/j.mrgentox.2018.07.003
PMID	30173861