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

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.