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We investigated the pulmonary and pleural toxicity of <jats:styled-content style=\"fixed-case\">POT<\/jats:styled-content> fibers with reference to 2 non\u2010fibrous titanium dioxide nanoparticles (<jats:styled-content style=\"fixed-case\">nTiO<\/jats:styled-content><jats:sub>2<\/jats:sub>), photoreactive anatase (a\u2010<jats:styled-content style=\"fixed-case\">nTiO<\/jats:styled-content><jats:sub>2<\/jats:sub>) and inert rutile (r\u2010<jats:styled-content style=\"fixed-case\">nTiO<\/jats:styled-content><jats:sub>2<\/jats:sub>). Ten\u2010week\u2010old male F344 rats were given 0.5 <jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content> of 250 \u03bcg\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content> suspensions of <jats:styled-content style=\"fixed-case\">POT<\/jats:styled-content> fibers, a\u2010<jats:styled-content style=\"fixed-case\">nTiO<\/jats:styled-content><jats:sub>2<\/jats:sub>, or r\u2010<jats:styled-content style=\"fixed-case\">nTiO<\/jats:styled-content><jats:sub>2<\/jats:sub>, 8 times (1 mg\/rat) over a 15\u2010day period by trans\u2010tracheal intrapulmonary spraying (<jats:styled-content style=\"fixed-case\">TIPS<\/jats:styled-content>). Rats were killed at 6 hours and at 4 weeks after the last <jats:styled-content style=\"fixed-case\">TIPS<\/jats:styled-content> dose. Alveolar macrophages were significantly increased in all treatment groups at 6 hours and at 4 weeks. At week 4, a\u2010<jats:styled-content style=\"fixed-case\">nTiO<\/jats:styled-content><jats:sub>2<\/jats:sub> and r\u2010<jats:styled-content style=\"fixed-case\">nTiO<\/jats:styled-content><jats:sub>2<\/jats:sub> were largely cleared from the lung whereas a major fraction of <jats:styled-content style=\"fixed-case\">POT<\/jats:styled-content> fibers were not cleared. In the bronchoalveolar lavage, alkaline phosphatase activity was elevated in all treatment groups, and lactate dehydrogenase (<jats:styled-content style=\"fixed-case\">LDH<\/jats:styled-content>) activity was elevated in the a\u2010<jats:styled-content style=\"fixed-case\">nTiO<\/jats:styled-content><jats:sub>2<\/jats:sub> and <jats:styled-content style=\"fixed-case\">POT<\/jats:styled-content> groups. In lung tissue, oxidative stress index and proliferating cell nuclear antigen (<jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content>) index were elevated in the a\u2010<jats:styled-content style=\"fixed-case\">nTiO<\/jats:styled-content><jats:sub>2<\/jats:sub> and <jats:styled-content style=\"fixed-case\">POT<\/jats:styled-content> groups, and there was a significant elevation in C\u2010C motif chemokine ligand 2 (<jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>2) <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein in the <jats:styled-content style=\"fixed-case\">POT<\/jats:styled-content> group. In pleural cavity lavage, total protein was elevated in all 3 treatment groups, and <jats:styled-content style=\"fixed-case\">LDH<\/jats:styled-content> activity was elevated in the a\u2010<jats:styled-content style=\"fixed-case\">nTiO<\/jats:styled-content><jats:sub>2<\/jats:sub> and <jats:styled-content style=\"fixed-case\">POT<\/jats:styled-content> groups. Importantly, the <jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content> index of the visceral mesothelium was increased in the <jats:styled-content style=\"fixed-case\">POT<\/jats:styled-content> group. Overall, <jats:styled-content style=\"fixed-case\">POT<\/jats:styled-content> fibers had greater biopersistence, induced higher expression of <jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>2, and provoked a stronger tissue response than a\u2010<jats:styled-content style=\"fixed-case\">nTiO<\/jats:styled-content><jats:sub>2<\/jats:sub> or r\u2010<jats:styled-content style=\"fixed-case\">nTiO<\/jats:styled-content><jats:sub>2<\/jats:sub>.<\/jats:p>","DOI":"10.1111\/cas.13643","type":"journal-article","created":{"date-parts":[[2018,5,18]],"date-time":"2018-05-18T05:46:43Z","timestamp":1526622403000},"page":"2164-2177","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Potassium octatitanate fibers induce persistent lung and pleural injury and are possibly carcinogenic in male Fischer 344 rats"],"prefix":"10.1111","volume":"109","author":[{"given":"Mohamed","family":"Abdelgied","sequence":"first","affiliation":[{"name":"Nanotoxicology Project Nagoya City University Nagoya Japan"},{"name":"Department of Experimental Pathology and Tumor Biology Nagoya City University Graduate School of Medical Sciences Nagoya Japan"},{"name":"Department of Forensic Medicine and Toxicology Faculty of Veterinary Medicine Beni Suef University Beni\u2010Suef Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed M.","family":"El\u2010Gazzar","sequence":"additional","affiliation":[{"name":"Nanotoxicology Project Nagoya City University Nagoya Japan"},{"name":"Department of Experimental Pathology and Tumor Biology Nagoya City University Graduate School of Medical Sciences Nagoya Japan"},{"name":"Department of Forensic Medicine and Toxicology Faculty of Veterinary Medicine Alexandria University Alexandria 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