title: Long-Term Chronic Toxicity and Mesothelial Cell Reactions Induced by Potassium Octatitanate Fibers (TISMO) in the Left Thoracic Cavity in A/J Female Mice.
abstract: The present study was conducted to examine the chronic effects of potassium octatitanate fibers (trade name TISMO; chemical formula K2O·6TiO2) on the mouse lung and thoracic cavity. This method of infusion was employed to examine the direct effects of the fibers to the pleura. In the present study, 52- and 65-week experiments were employed to examine the long-term chronic effects after infusion of fiber-shaped TISMO into the thoracic cavities of A/J mice. Following this infusion, TISMO fibers were observed in the alveoli, indicating penetration through the visceral pleura. The additional histopathological detection of TISMO fibers in the liver, spleen, kidneys, ovary, heart, bone marrow, and brain of TISMO-infused mice indicated migration of the fibers out from the thoracic cavity. Atypical mesothelial cells with severe pleural proliferation were observed, but malignant mesotheliomas were not detected. This study demonstrated that intrathoracic infusion of TISMO fiber did not cause malignant mesothelioma but did cause severe chronic inflammation and proliferation of pleural mesothelial cells.
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Kagawa University, Kagawa, Japan yokohira@med.kagawa-u.ac.jp imaida@med.kagawa-u.ac.jp.
authors.forename: Masanao
authors.initials: M
authors.lastname: Yokohira
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Kagawa University, Kagawa, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Faculty of Medicine, Life Science Research Center, Kagawa University, Kagawa, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Kagawa University, Kagawa, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Kagawa University, Kagawa, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamakawa
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Kagawa University, Kagawa, Japan.
authors.forename: Sosuke
authors.initials: S
authors.lastname: Kishi
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Kagawa University, Kagawa, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Kanie
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Kagawa University, Kagawa, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Ninomiya
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Kagawa University, Kagawa, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Saoo
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Kagawa University, Kagawa, Japan yokohira@med.kagawa-u.ac.jp imaida@med.kagawa-u.ac.jp.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imaida
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced / Q000175:diagnosis; D008654:Mesothelioma / Q000139:chemically induced / Q000175:diagnosis; D000086002:Mesothelioma, Malignant; D051379:Mice; D008805:Mice, Inbred A; D009929:Organ Size / Q000187:drug effects; D010994:Pleura / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D035423:Thoracic Cavity / Q000187:drug effects* / Q000378:metabolism; D014025:Titanium / Q000633:toxicity*; D036401:Toxicity Tests, Chronic
chemical_list: C021028:potassium octatitanate; D014025:Titanium
keywords: TISMO; TiO2; lung; mesothelioma; mouse; tumorigenesis