TiO2 Nanoparticles Caused DNA Damage in Lung and Extra-Pulmonary Organs Through ROS-Activated FOXO3a Signaling Pathway After Intratracheal Administration in Rats

被引：27

作者：

Han, Bin ^{[1
]}

Pei, Zijie ^{[2
]}

Shi, Lei ^{[3
]}

Wang, Qian ^{[4
]}

Li, Chen ^{[1
]}

Zhang, Boyuan ^{[1
]}

Su, Xuan ^{[1
]}

Zhang, Ning ^{[1
]}

Zhou, Lixiao ^{[1
]}

Zhao, Bo ^{[5
]}

Niu, Yujie ^{[3
,6
]}

Zhang, Rong ^{[1
,6
]}

机构：

[1] Hebei Med Univ, Dept Toxicol, 361 Zhongshan East Rd, Shijiazhuang 050017, Hebei, Peoples R China

[2] China Three Gorge Univ, Sch Med, Dept Pathol, Yichang 443002, Peoples R China

[3] Hebei Med Univ, Occupat Hlth & Environm Hlth, Shijiazhuang 050017, Hebei, Peoples R China

[4] Hebei Med Univ, Expt Ctr, Shijiazhuang 050017, Hebei, Peoples R China

[5] Hebei Med Univ, Dept Lab Diag, Shijiazhuang 050017, Hebei, Peoples R China

[6] Hebei Med Univ, Hebei Key Lab Environm & Human Hlth, Shijiazhuang 050017, Hebei, Peoples R China

来源：

INTERNATIONAL JOURNAL OF NANOMEDICINE | 2020年 / 15卷

基金：

中国国家自然科学基金;

关键词：

Nano-TiO2; DNA damage; PI3K/AKT/FOXO3a signaling pathway; DNA repair; GADD45 alpha/ChK2/XRCC1 signaling pathway; TITANIUM-DIOXIDE NANOPARTICLES; TRANSCRIPTION FACTOR FOXO3A; OXIDATIVE-STRESS; REDOX REGULATION; OCCUPATIONAL-EXPOSURE; CELL-SURVIVAL; SIZED TIO2; GENOTOXICITY; REPAIR; LIVER;

D O I：

10.2147/IJN.S254969

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Introduction: Because of the increased production and application of manufactured Nano-TiO2 in the past several years, it is important to investigate its potential hazards. TiO2 is classified by IARC as a possible human carcinogen; however, the potential mechanism of carcinogenesis has not been studied clearly. The present study aimed to investigate the mechanism of DNA damage in rat lung and extra-pulmonary organs caused by TiO2 nanoparticles. Methods: In the present study, SD rats were exposed to Nano-TiO2 by intratracheal injection at a dose of 0, 0.2, or 1 g/kg body weight. The titanium levels in tissues were detected by ICP-MS. Western blot was used to detect the protein expression levels. The DNA damage and oxidative stress were detected by comet assay and ROS, MDA, SOD, and GSH-Px levels, respectively. Results: The titanium levels of the 1 g/kg group on day-3 and day-7 were significantly increased in liver and kidney as well as significantly decreased in lung compared to day-1. ROS and MDA levels were statistically increased, whereas SOD and GSH-Px levels were statistically decreased in tissues of rats in dose-dependent manners after Nano-TiO2 treatment. PI3K, p-AKT/AKT, and p-FOXO3a/FOXO3a in lung, liver, and kidney activated in dose-dependent manners The levels of DNA damage in liver, kidney, and lung in each Nano-TiO2 treatment group were significantly increased and could not recover within 7 days. GADD45 alpha, ChK2, and XRCC1 in liver, kidney, and lung of rats exposed to Nano-TiO2 statistically increased, which triggered DNA repair. Conclusion: This work demonstrated that Ti could deposit in lung and enter extra-pulmonary organs of rats and cause oxidative stress, then trigger DNA damage through activating the PI3K-AKT-FOXO3a pathway and then promoting GADD45 alpha, ChK2, and XRCC1 to process the DNA repair.

引用

页码：6279 / 6294

页数：16

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