Strain differences in pleural mesothelial cell reactions induced by potassium octatitanate fibers (TISMO) infused directly into the thoracic cavity

Our plain-English summary of Strain differences in pleural mesothelial cell reactions induced by potassium octatitanate fibers (TISMO) infused directly into the thoracic cavity, by M. Yokohira, Y. Nakano, K. Yamakawa, et al (Experimental and Toxicologic Pathology, 2013).

The study

• Authors: M. Yokohira, Y. Nakano, K. Yamakawa, S. Kishi, F. Ninomiya, K. Saoo, K. Imaida
• Journal: Experimental and Toxicologic Pathology
• Published: 2013;65(6):925-32
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Although we have previously reported that the fiber-shaped TISMO, morphologically similar to asbestos, can induce a severe mesothelial reaction in A/J mice, it is important to clarify any strain differences. In the present study, female A/J, C3H/HeN, ICR and C57BL/6 mice were therefore employed as test strains. At the beginning of the experiment, all mice underwent a left thoracotomy and direct administration of 3mg of TISMO particles suspended in 0.2 ml saline into the left thorax. The experiment was terminated after 21 weeks and all groups were sacrificed and the mesothelium and main organs were examined histopathologically. To contribute to mechanistic analysis, iron staining with Berlin blue and Turnbull's blue, and immunostaining for calretinin were also performed. The present experiment demonstrated only minor strain differences in the degree of pleural reaction to TISMO. However, there was clear variation in the iron and lymphocyte accumulation in the pleura and in the liver. This difference in response to TISMO fibers in vivo is important information when considering the development of mesothelioma as an animal model and the extrapolation to human risk from such animal studies.

Copyright © 2013 Elsevier GmbH. All rights reserved.

In plain English

This animal experiment from Kagawa University in Japan tested whether mouse strains react differently to potassium octatitanate fibers (TISMO), which the authors describe as shaped like asbestos. No asbestos was tested. Sixty-four female mice, 16 each of the A/J, ICR, C3H/HeN and C57BL/6 strains, had 3 mg of TISMO in saline placed into the left chest cavity during surgery. Five died just after surgery, from surgery or anesthesia, and two at weeks 17 and 19; the other 57 were examined at 21 weeks. All strains developed thickened, fiber-containing pleura, without significant strain differences in absolute maximum thickness. Mesothelial cells gathered in the thickened pleura about equally in all strains. Some showed mild atypia, but there was no evidence of malignancy. Strains differed in iron deposits and lymphocyte infiltration. ICR mice showed the most iron and marked lymphocyte infiltration in the pleura, and C57BL/6 mice the least iron. Fibers also appeared in the liver of all strains. The authors concluded that this strain variation matters for animal models of mesothelioma. They noted that, for wild-type animals, 21 weeks appears too short to produce malignant lesions.

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 comparing four mouse strains given TISMO fibers directly into the chest cavity
• Who was studied: 64 female mice aged 7 weeks, 16 each of the A/J, ICR, C3H/HeN and C57BL/6 strains, kept at Kagawa University, Japan. Seven died before the end of the study. Final group sizes were 15, 16, 12 and 14 (57 mice).
• Exposure: A single dose of 3 mg of potassium octatitanate fibers (TISMO; fibers mostly shorter than 50 micrometres long and less than 2 micrometres wide) in 0.2 ml saline, put into the left chest cavity through a thoracotomy. The experiment ended after 21 weeks. No asbestos fiber was used.
• Main results:
  • Five mice died just after the thoracotomy (3 C3H/HeN, 2 C57BL/6). The authors attributed these deaths to the surgery or anesthesia.
  • Two more mice died before sacrifice: 1 C3H/HeN at week 17 and 1 A/J at week 19. The article then states that these deaths were considered accidental.
  • Absolute maximum visceral pleural thickness did not differ significantly between the strains. Table 2 values: A/J 0.32 ± 0.11 mm, ICR 0.29 ± 0.12 mm, C3H/HeN 0.31 ± 0.07 mm, C57BL/6 0.29 ± 0.15 mm.
  • When thickness was divided by lung weight, A/J pleura were significantly thicker (1.49 ± 0.66) than ICR pleura (0.78 ± 0.50 in the text; 0.78 ± 0.20 in Table 2).
  • Mesothelial cells, confirmed by calretinin staining, infiltrated the thickened pleura to almost the same degree in all strains. Some showed mild atypia, but none showed malignancy, invasion or metastasis.
  • Lymphoid cell infiltration into the thickened pleura was marked in ICR mice.
  • Ferric iron (Berlin blue stain) was found in thickened pleura with fibers in all strains. ICR mice had the strongest accumulation and C57BL/6 mice the least.
  • No lesions in any group stained positive for ferrous iron (Turnbull's blue).
  • Fibers believed to be TISMO were found in the liver in all groups. C3H/HeN mice had much less liver lymphocyte infiltration than the other strains.
  • Ferric iron around fibers in the liver was strong in ICR and C3H/HeN mice and weak in A/J and C57BL/6 mice.
• The authors' conclusion: The authors concluded that there were no unequivocal strain differences in pleural thickening in response to TISMO fibers. There was, however, clear strain variation in iron and lymphocyte accumulation in the pleura and liver, which they considered relevant to developing animal models of mesothelioma and to extrapolating to human risk.
• Limitations the authors state:
  • The authors stated that, for wild-type animals, 21 weeks appears too short to induce malignant lesions, and that longer experiments are needed.
  • The authors stated that lung weight is not fully reliable for correcting pleural thickness, because of exfoliation and severe adhesion to the chest wall.

Topics

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

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