title: Reduction of DNA damage induced by titanium dioxide nanoparticles through Nrf2 in vitro and in vivo.
abstract: Titanium dioxide nanoparticles (Nano-TiO2) are widely used to additives in cosmetics, pharmaceutical, paints and foods. Recent studies have demonstrated that Nano-TiO2 induces DNA damage and increased the risk of cancer and the mechanism might relate with oxidative stress. The aim of this study was to evaluate the effects of Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), an anti-oxidative mediator, on DNA damage induced by Nano-TiO2. Wildtype, Nrf2 knockout (Nrf2(-/-)) and tert-butylhydroquinone (tBHQ) pre-treated HepG2 cells and mice were treated with Nano-TiO2. And then the oxidative stress and DNA damage were evaluated. Our data showed that DNA damage, reactive oxygen species (ROS) generation and MDA content in Nano-TiO2 exposed cells were significantly increased than those of control in dose dependent manners. Nrf2/ARE droved the downstream genes including NAD(P)H dehydrogenase [quinine] 1(NQO1), heme oxygenase 1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC) expression were significantly higher in wildtype HepG2 cells after Nano-TiO2 treatment. After treatment with Nano-TiO2, the DNA damages were significantly increased in Nrf(-/-) cells and mice whereas significantly decreased in tBHQ pre-treatment cells and mice, compared with the wildtype HepG2 cells and mice, respectively. Our results indicated that the acquired of Nrf2 leads to a decreased susceptibility to DNA damages induction by Nano-TiO2 and decreasing of risk of cancer which would provide a strategy for a more efficacious sensitization of against of Nano-TiO2 toxication.
authors.affiliation: Department of Toxicology, Hebei Medical University, Shijiazhuang, China; Department of Laboratory Diagnosis, Hebei Medical University, Shijiazhuang, China.
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Occupational Health and Environmental Health, Hebei Medical University, Shijiazhuang, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Toxicology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Occupational Health and Environmental Health, Hebei Medical University, Shijiazhuang, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Toxicology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Huicai
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Toxicology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Toxicology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Hebei Keylab of Laboratory Animal Science, Shijiazhuang, China.
authors.forename: Shufeng
authors.initials: S
authors.lastname: Liu
authors.affiliation: Hebei Keylab of Laboratory Animal Science, Shijiazhuang, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Xiumen Community Health Service Centre, Shijiazhuang, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Toxicology, Hebei Medical University, Shijiazhuang, China; Hebei Keylab of Laboratory Animal Science, Shijiazhuang, China. Electronic address: rongzhang@hebmu.edu.cn.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D061745:Antioxidant Response Elements; D002460:Cell Line; D004249:DNA Damage; D005260:Female; D006801:Humans; D006873:Hydroquinones; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D017382:Reactive Oxygen Species; D014025:Titanium / Q000633:toxicity*
chemical_list: D006873:Hydroquinones; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; C009495:titanium dioxide; C018855:2-tert-butylhydroquinone; D014025:Titanium
keywords: DNA damage; Nanoparticles; Nrf2; Oxidative stress; Titanium dioxide