title: Chronic nasal exposure to nanoparticulate TiO2causes pulmonary tumorigenesis in male mice.
abstract: Chronic inhalation bioassays in rodents are used to assess pulmonary carcinogenicity for purposes of hazard identification and potentially for risk characterization. Numerous studies have been confirmed that exposure to titanium dioxide nanoparticles (TiO2NPs) may result in chronic pulmonary inflammation in both mice and rats. However, very few studies have focused on the pulmonary tumorigenesis. In this study, to examine whether chronic TiO2NP exposure induce tumorigenesis in the lung, forty mice (each group) were nasally exposed to 1.25, 2.5, and 5 mg/kg body weight TiO2NPs for nine consecutive months, lung pathology was then evaluated, and the biochemical function parameters in bronchoalveolar lavage (BAL) and tumor markers in the serum were investigated using an ELISA method. We observed that nasal exposure to TiO2NPs caused infiltration of inflammatory cells, tumorigenesis in the lung, and accompanied by significant increases of lactate dehydrogenase, alkaline phosphatase, and total protein levels in BLAF, significant increases in tumor markers including cytokeratin 19, neuron-specific enolase, carcinoembryonic antigen, squamous cell carcinoma antigen, and cancer antigen-125 in the serum. It implies that chronic inhaled TiO2NPs may increase possibility of pulmonary tumor formation for human. Therefore, the production and application of TiO2NPs should be paid more attention. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1651-1657, 2017.
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Food Safety and Nutritional Function, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Food Safety and Nutritional Function, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ji
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Food Safety and Nutritional Function, Huaiyin Normal University, Huaian, 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University, Huaian, 223300, China.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Library of Soochow University, Suzhou, China, Suzhou, 215123, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects*; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000276:immunology; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology; D014025:Titanium / Q000008:administration & dosage* / Q000633:toxicity*; D036401:Toxicity Tests, Chronic
chemical_list: C009495:titanium dioxide; D014025:Titanium
keywords: chronic inhaled exposure; mice; pulmonary tumorigenesis; titanium dioxide nanoparticles; tumor markers