Potassium octatitanate fibers (TISMO) induce pleural mesothelial cell reactions with iron accumulation in female A/J mice

Our plain-English summary of Potassium octatitanate fibers (TISMO) induce pleural mesothelial cell reactions with iron accumulation in female A/J mice, by M. Yokohira, N. Hashimoto, K. Yamakawa, et al (Oncology Letters, 2010).

The study

• Authors: M. Yokohira, N. Hashimoto, K. Yamakawa, S. Suzuki, K. Saoo, T. Kuno, K. Imaida
• Journal: Oncology Letters
• Published: 2010;1(4):589-594
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

It is crucial to develop therapeutic approaches for malignant mesothelioma, as well as to obtain information involving the possible mechanism involved in the development of mesothelioma. Subsequently, thoracotomy was performed to infuse test particles directly into the thoracic cavity of A/J mice. Fiber-shaped particles of potassium octatitanate (TISMO) and granular-shaped micro- and nano-size order particles of titanium dioxide (TiO(2)) were employed (1.5 mg in 0.2 ml saline/mouse). The experiment was terminated after 21 weeks to assess responses. Only the fiber-shaped TISMO, morphologically similar to asbestos, induced a severe reaction of the pleura. A number of TISMO fibers were observed in the alveoli, indicating penetration through the pleura. Following Berlin blue staining, positive spots were observed around the TISMO fibers, indicative of iron. These positive spots corresponded with cells that immunostained positively for calretinin, a marker of mesothelial cells. Similar observations were reported for asbestos-induced mesothelioma. The present study showed that only fiber-shaped TISMO induced severe reactions of the mesothelium in the pleura, and these involved iron accumulation derived from endogenous sources. The results indicate that the risk of mesothelial cell reaction does not depend on particle size, but may depend on shape.

In plain English

In this animal experiment, female A/J mice had 1.5 mg of a titanium-based material placed surgically into the left chest cavity: fiber-shaped potassium octatitanate (TISMO), granular titanium dioxide (under 5 µm) or nano-size titanium dioxide (about 80 nm). Controls received saline or no treatment. No asbestos was tested. After 21 weeks, pleural thickening was found in 20 of 20 TISMO-treated mice, compared with 1 of 14 nano-size titanium dioxide mice, 2 of 14 granular titanium dioxide mice, 0 of 15 saline-treated and 0 of 5 untreated mice. TISMO-treated mice had severe adhesions of the lung to the chest wall, and fibers appeared in the air sacs. Iron staining appeared around TISMO fibers in the thickened pleura, alongside cells marked as mesothelial cells. Because TISMO contains no iron, the authors judged the iron likely came from the body. No statistically significant difference in lung adenomas was detected between groups. The authors concluded that the reaction may depend on particle shape rather than size. They found it difficult to diagnose malignant pleural mesothelioma, as the cells showed only slight atypia.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: test particles infused directly into the left chest cavity of mice through a surgical opening (thoracotomy), with saline-treated and untreated control groups
• Who was studied: 70 female A/J mice, 7 weeks old at the start, at Kagawa University, Japan. Groups: TISMO (20), titanium dioxide nano (15), titanium dioxide micro (15), saline control (15) and untreated without surgery (5). Two mice died after surgery, one in each titanium dioxide group.
• Exposure: A single dose of 1.5 mg in 0.2 ml saline into the left chest cavity. Materials: fiber-shaped potassium octatitanate (TISMO), with fibers mostly under 50 µm long and under 2 µm wide; granular titanium dioxide (rutile) under 5 µm; and nano-size titanium dioxide of about 80 nm. No asbestos was used.
• Main results:
  • Pleural thickening was found in 20/20 TISMO-treated mice, 1/14 nano titanium dioxide mice, 2/14 micro titanium dioxide mice, 0/15 saline controls and 0/5 untreated mice. TISMO fibers in the air sacs (alveoli) were found in 20/20 TISMO mice and in no other group. Both differences were statistically significant compared with the other groups.
  • Severe adhesions of the lung to the chest wall were seen in the TISMO group. Adhesions were less or absent in the titanium dioxide groups. The control groups had no inflammatory lesions.
  • In the TISMO group, positive spots on iron (Berlin blue) staining were found in the thickened pleura around the fibers. They were not found in the alveoli or in any other group.
  • Cells staining positive for calretinin, a marker of mesothelial cells, were found in essentially the same lesions as the iron spots.
  • TISMO contains no iron, so the authors considered the accumulated iron likely to come from the body itself.
  • Particle deposits were found in lymph nodes around the lungs in 15/20 TISMO, 13/14 nano titanium dioxide and 14/14 micro titanium dioxide mice, and in none of the controls.
  • Lung adenomas occurred in all groups: 3/20 TISMO, 5/14 nano titanium dioxide, 1/14 micro titanium dioxide, 2/15 saline and 1/5 untreated. No statistically significant difference between groups was detected.
• The authors' conclusion: The authors concluded that only fiber-shaped TISMO caused severe reactions of the pleural mesothelium, and that these involved iron accumulation from the body's own sources. They stated that the risk of mesothelial cell reaction does not depend on particle size but may depend on shape.
• Limitations the authors state:
  • The mesothelial cells showed only slight atypia, and a diagnosis of malignant pleural mesothelioma was difficult to make.
  • The 21-week experimental period may have been too short, and longer studies are needed.
  • Female mice were used, although human mesothelioma cases are mostly male. The authors recommend male mice for future mesothelioma experiments.
  • TISMO contains K2O and so differs chemically from titanium dioxide, which means the comparison was not purely one of shape. The authors suggest future tests using fiber-shaped and fine particles of identical chemical composition.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Malignant Mesothelioma, Mesothelioma, Thoracotomy, Pleura, Alveoli, Calretinin, Mesothelium.

Related studies

• Strain differences in pleural mesothelial cell reactions induced by potassium octatitanate fibers (TISMO) infused directly into the thoracic cavity — M. Yokohira, Y. Nakano, et al. (2013)
• Chronic mesothelial reaction and toxicity of potassium octatitanate fibers in the pleural cavity in mice and F344 rats — M. Yokohira, Y. Nakano-Narusawa, et al. (2016)
• Potassium octatitanate fibers induce persistent lung and pleural injury and are possibly carcinogenic in male Fischer 344 rats — M. Abdelgied, A.M. El-Gazzar, et al. (2018)
• Carcinogenic effect of potassium octatitanate (POT) fibers in the lung and pleura of male Fischer 344 rats after intrapulmonary administration — M. Abdelgied, A.M. El-Gazzar, et al. (2019)
• Pulmonary and pleural toxicity of potassium octatitanate fibers, rutile titanium dioxide nanoparticles, and MWCNT-7 in male Fischer 344 rats — M. Abdelgied, A.M. El-Gazzar, et al. (2019)
• Asbestos body formation and iron accumulation in mouse peritoneal granulomas after the introduction of crocidolite asbestos fibers — H.K. Koerten, J. Hazekamp, et al. (1990)

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