title: Genotoxic evaluation of titanium dioxide nanoparticles in vivo and in vitro.
abstract: With the extensive application of titanium dioxide (TiO2) nanoparticles (NPs) in food industry, there is a rising debate concerning the possible risk associated with exposure to TiO2 NPs. The purpose of this study is to evaluate the genotoxicity of TiO2 NPs using in vivo and in vitro test systems. In vivo study, the adult male Sprague-Dawley rats were exposed to anatase TiO2 NPs (75 ± 15 nm) through intragastric administration at 0, 10, 50 and 200mg/kg body weight every day for 30 days. The γ-H2AX assay showed TiO2 NPs could induce DNA double strand breaks in bone marrow cells after oral administration. However, the micronucleus test revealed that the oral-exposed TiO2 NPs did not cause damage to chromosomes or mitotic apparatus observably in rat bone marrow cells. In vitro study, Chinese hamster lung fibroblasts (V79 cells) were exposed to TiO2 NPs at the dose of 0, 5, 10, 20, 50 and 100 μg/mL. Significant decreases in cell viability were detected in all the treated groups after 24h and 48h exposure. Significant DNA damage was only observed at the concentration of 100 μg/mL after 24h treatment using the comet assay. The obvious gene mutation was observed at the concentration of 20 and 100 μg/mL after 2h treatment using hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene mutation assay. This study presented a comprehensive genotoxic evaluation of TiO2 NPs, and TiO2 NPs were shown to be genotoxic both in vivo and in vitro tests. The gene mutation and DNA strand breaks seem to be more sensitive genetic endpoints for the detection of TiO2 NPs induced genotoxic effects.
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China. Electronic address: czjczj01@163.com.
authors.forename: Zhangjian
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China. Electronic address: wangyun@bjmu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China. Electronic address: bate@bjmu.edu.cn.
authors.forename: Te
authors.initials: T
authors.lastname: Ba
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China. Electronic address: liyangbjmu@bjmu.edu.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China. Electronic address: puji328@bjmu.edu.cn.
authors.forename: Ji
authors.initials: J
authors.lastname: Pu
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China. Electronic address: chentian@bjmu.edu.cn.
authors.forename: Tian
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China. Electronic address: sys_850827@163.com.
authors.forename: Yanshuang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China. Electronic address: fsh200901@126.com.
authors.forename: Yongen
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China. Electronic address: helenqianqin@bjmu.edu.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: Qian
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China. Electronic address: goodboylinlin@163.com.
authors.forename: Jinglin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, China. Electronic address: jiaguangjia@bjmu.edu.cn.
authors.forename: Guang
authors.initials: G
authors.lastname: Jia
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D009154:Mutation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014025:Titanium / Q000633:toxicity*
chemical_list: C009495:titanium dioxide; D014025:Titanium; D007041:Hypoxanthine Phosphoribosyltransferase
keywords: Chromosome damage; DNA damage; Gene mutation; Genetic endpoint; Genotoxicity; Titanium dioxide nanoparticles