title: Chronic mesothelial reaction and toxicity of potassium octatitanate fibers in the pleural cavity in mice and F344 rats.
abstract: Fiber-shaped particles of potassium octatitanate (tradename TISMO; chemical formula K2 O·6TiO2 ), which are morphologically similar to asbestos particles, were shown to induce severe proliferative reactions in the pleural mesothelium in a previous experiment carried out over 21 weeks. The present study aims to determine whether these fibers induce malignant mesotheliomas in rodents, and to examine chronic toxicity induced. Additionally, we investigated the specific differences observable between the biological responses to the direct infusion of the fibers alone into the pleural cavity and those induced by the co-administration of the fibers with a known carcinogen. To detect the induction of malignant pleural mesotheliomas, two experiments were undertaken. In Experiment 1, four strains of mice, A/J, C3H, ICR, and C57BL, were examined for 52 weeks after experimental treatment with TISMO. In Experiment 2, the F344 rats were treated with TISMO alone, the lung carcinogen N-bis (2-hydroxypropyl) nitrosamine (DHPN) alone, both TISMO and DHPN, or left untreated and were then examined for 52 weeks. In this experiment, malignant lesion induction was expected in the co-administration group. TISMO fibers were observed in the alveoli, indicating penetration through the visceral pleura in mice and rats. The histopathological detection of TISMO fibers in the liver and kidneys of mice and rats indicated migration of the fibers out of the pleural cavity. Atypical mesothelial cells with severe pleural proliferation were observed, but malignant mesotheliomas were not detected. Among the rats, there were no observed malignant alterations in the mesothelium induced by DHPN-TISMO co-administration.
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.
authors.forename: Masanao
authors.initials: M
authors.lastname: Yokohira
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakano-Narusawa
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamakawa
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Kanie
authors.affiliation: Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imaida
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009602:Nitrosamines / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D035422:Pleural Cavity / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*
chemical_list: D009602:Nitrosamines; C012457:diisopropanolnitrosamine; C021028:potassium octatitanate; D014025:Titanium
keywords: DHPN; TISMO; mesothelioma; mouse; rat