The histopathology and ultrastructure of pleural mesotheliomas produced in the rat by injections of crocidolite asbestos

Our plain-English summary of The histopathology and ultrastructure of pleural mesotheliomas produced in the rat by injections of crocidolite asbestos, by J.M. Davis (British Journal of Experimental Pathology, 1979).

The study

• Author: J.M. Davis
• Journal: British Journal of Experimental Pathology
• Published: 1979;60(6):642-52
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Primary tumours of the pleural cavity were produced in rats by the intrapleural injection of crocidolite asbestos. Their histological structure as seen with both light and electron microscopy was very variable and tumours frequently contained elements of both connective-tissue and epithelial type. In some instances the connective-tissue elements predominated from the start and the earliest tumour nodules consisted mainly of pleomorphic connective-tissue cells with only a few layers of cells more nearly epithelial in type on the surface. This pattern was largely retained when tumour nodules increased in size and coalesced, but in the deeper layers of advanced tumours the pleomorphic connective-tissue pattern was often replaced by a more uniform spindle-cell form. Other tumours were more predominantly epithelial in type, showing either a papillary pattern with rounded epithelial cells growing in solid columns, or a vesicular form in which large tissue spaces, often intracellular, were lined by very thin layers of extended cell cytoplasm. Whereas early tumours showed only one histological pattern, the more advanced stages often exhibited areas of all 3, so that there seemed to be some degree of histological mutability. The spindle-cell areas of advanced tumours frequently showed evidence of direct invasion of the surrounding tissue but this was never seen with the epithelial forms of rat mesothelioma.

In plain English

This was an animal experiment. Forty-eight white Han rats were each given one injection of 25 mg of crocidolite asbestos into the pleural cavity, the space around the lungs. The rats were killed 12 to 20 months later, and tumours and possible early lesions were examined with light and electron microscopes. Tumours, including very early growths confirmed only under the microscope, developed in 16 of the 48 rats (33%). The pleural mesotheliomas showed three distinct tissue patterns, visible even in the earliest lesions. One had epithelial-type cells on the surface over spindle-shaped connective-tissue cells. One was papillary, with rounded epithelial cells in solid columns. One was vesicular, with spaces lined by thin, flattened cells. Nodules under 1 mm showed only one pattern, while larger tumours often showed more than one. Spindle-cell areas often invaded the muscle of the body wall, but no invasion of lung tissue was found. Comparing these results with his earlier rat study, the author concluded that crocidolite appeared more carcinogenic in the peritoneal than the pleural cavity. He also concluded that mesotheliomas likely develop from basically mesenchymal cells.

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: intrapleural injection of asbestos in rats, followed by light and electron microscope examination of the resulting tumours
• Who was studied: 48 white Han rats, killed at intervals from 12 to 20 months after injection (Institute of Occupational Medicine, Edinburgh)
• Exposure: A single intrapleural injection of 25 mg of UICC crocidolite asbestos suspended in sterile saline
• Main results:
  • Tumours, including very early growths confirmed only after histological sectioning, developed in 16 of the 48 injected rats (33%)
  • The pleural mesotheliomas showed 3 distinct histological patterns, which could be seen in the earliest lesions
  • One pattern was papillary, with rounded epithelial cells growing in solid columns
  • Another pattern was vesicular, with multiple tissue spaces lined by greatly extended, flattened epithelial cells; some of these spaces were inside single cells
  • All small tumour nodules below 1 mm showed only one pattern, while larger nodules and confluent tumour areas frequently showed more than one
  • 3 solitary tumours consisted entirely of spindle cells and looked very similar to benign fibromas
  • The epithelial varieties showed no tendency to metastasize. Apart from the 3 solitary tumours, spindle-cell areas frequently invaded the muscle coating of the body wall. No direct invasion of lung tissue was found.
• The authors' conclusion: The author compared these results with his earlier study of rats given the same dose into the peritoneal cavity. He concluded that crocidolite appeared more carcinogenic, and quicker to act, in the peritoneal than the pleural cavity. He also concluded that mesothelial lining cells and all tumours classified as mesotheliomas likely develop from basically mesenchymal cells.
• Limitations the authors state:
  • Because the large spaces in vesicular tumours were seldom fully contained in one electron microscope section, the author could not be certain what proportion of them were inside cells
  • The author could not rule out that the spindle-cell elements in advanced epithelial tumours were a separate example of neoplastic change rather than derived from epithelial tumour cells

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Histopathology, Pleural Mesothelioma, Crocidolite, Pleural Cavity, Pleomorphic, Mesothelioma.

Related studies

• Acute and chronic effects of intraperitoneal injection of two types of asbestos in rats with a study of the histopathogenesis and ultrastructure of resulting mesotheliomas — M.L. Shin, H.I. Firminger (1973)
• Ultrastructure of mesothelial regeneration after intraperitoneal injection of asbestos fibres on rat omentum — S. Gonzalez, J. Friemann, et al. (1991)
• Histogenesis and fine structure of peritoneal tumors produced in animals by injections of asbestos — J.M. Davis (1974)
• The calcification of fibrous pleural lesions produced in guinea-pigs by the injection of chrysotile asbestos dust — J.M. Davis (1971)
• Ultrastructure of the lung in the rat following exposure to crocidolite asbestos and quartz — K. Miller, I. Webster, et al. (1978)
• Further observations on the ultrastructure and chemistry of the formation of asbestos bodies — J.M. Davis (1970)

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