Pathogenesis of experimentally induced asbestos mesothelioma in rats

Our plain-English summary of Pathogenesis of experimentally induced asbestos mesothelioma in rats, by L.A. Vasilieva, L.N. Pylev, Y.A. Rovensky (Cancer Letters, 1998).

The study

• Authors: L.A. Vasilieva, L.N. Pylev, Y.A. Rovensky
• Journal: Cancer Letters
• Published: 1998;134(2):209-16
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Fragments of parietal and visceral pleura were studied by total films preparation, light microscopy and SEM at different times after intrapleural injection of asbestos in Wistar rats. Pleural rat mesothelium in histological slices consists normally of one layer of oblong cells. By SEM the cells are flat and coated with microvilli of different lengths. In total films the parietal mesothelium was composed of large polygonal cells covering intercostal spaces and small cells covering spaces over the ribs. Inflammatory reaction and permanent pathological regenerative processes were observed in the mesothelium during 24 months after inoculation of asbestos fibres. Different lesions which we regarded as preneoplastic or premesotheliomatous were observed against the background of or without these processes. They were diffuse irregular hyperplasia and proliferation of epithelium-like or fibroblast-like cells and focal nodous proliferates composed of such cells with various morphological structures. The number of thymidine-labelled cells was significantly more inside the proliferates than in the surrounding tissue. They were confirmed by SEM and histological slices of the same fields. Chronic pathological regeneration of pleural mesothelium could be the background against which preneoplastic lesions and mesotheliomas develop easily.

In plain English

This animal experiment in Wistar rats examined how the chest-cavity lining (pleural mesothelium) changed after asbestos was injected into the pleural space. The authors used three methods. First, ordinary tissue slides from dying and dead rats in experiments with various asbestos types, erionite and glass fibres. Second, whole sheets of lining (total films) from 60 female rats given three injections of 20 mg of UICC Rhodesian chrysotile, compared with 60 control rats. Third, scanning electron microscopy after one or three injections of UICC Rhodesian or Russian chrysotile. Within 24 hours the lining was damaged and inflamed. Over 24 months, cells with many nuclei persisted, and dividing cells were more frequent than in controls, signs the authors took as continuing damage and repair. They described diffuse and nodular overgrowths of lining cells, which they regarded as preneoplastic. Nodular overgrowths could develop without diffuse overgrowth. From 6 to 7 months on, 8 to 10% of cells in large-cell zones took up a marker of DNA synthesis. In clusters of uniform cells the figure was 30 to 50%. The authors concluded that chronic regeneration appeared to be a background for preneoplastic lesions and mesotheliomas.

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 (morphological study of rat pleura using histological slices, mesothelium total film preparations with [3H]thymidine labelling, and scanning electron microscopy)
• Who was studied: Wistar rats in Moscow, Russia. The total-film part used 60 female rats injected with asbestos and 60 female control rats. Five experimental and 5 control rats were killed at each of 1, 3, 6, 12, 15 and 24 months after the last injection. The histological slides came from dying and dead male and female Wistar rats in earlier fibre experiments. Animal numbers for the electron microscopy part are not given.
• Exposure: Total films: intrapleural injection of 20 mg UICC Rhodesian chrysotile, described as given 'three times monthly'. Electron microscopy: a single injection, or three injections at 1-month intervals, of 20 mg UICC Rhodesian or Russian chrysotile. Histological slides: experiments with different Russian and UICC asbestos, erionite and glass fibres.
• Main results:
  • In the histological slides from experiments with different fibres, the timing and degree of the changes considered preneoplastic were similar and corresponded to carcinogenic strength.
  • Focal (nodular) hyperplasia appeared earlier, at 5 to 8 months, in rats exposed to erionite, and much later in rats given glass fibres.
  • In chrysotile-exposed rats, cells with an increased number of nuclei and symplasts (10 or more nuclei) were found throughout the 24-month observation period.
  • The number of mitoses (dividing cells) was higher in experimental animals than in control animals at all time periods.
  • Results of [3H]thymidine labelling in exposed rats from 6 to 7 months on: the label index was about 0.05% in small-cell zones, 8 to 10% in large-cell zones, and 10 to 16% in zones with multinuclear elements. In foci of uniform round or elongated cells, the label index was 30 to 50%.
  • By scanning electron microscopy, 24 hours after injection the mesothelial layer, basal membrane and underlying tissue showed destruction, and inflammation developed.
  • At 16 to 22 months after injection, pleural sclerosis, inflammation and mesothelial destruction were seen alongside preneoplastic mesothelial changes and tumours.
  • The authors distinguished two preneoplastic stages, diffuse and nodular mesothelial hyperplasia. Focal proliferations could develop without diffuse hyperplasia.
  • No regular relationship was found between where asbestos accumulated and where mesothelial cells proliferated.
• The authors' conclusion: The authors concluded that the persistent regeneration after asbestos exposure might be considered pathological. They also concluded that chronic regenerative processes in the mesothelium appeared to be a background for preneoplastic lesions (diffuse and nodular hyperplasia) and mesotheliomas.
• Limitations the authors state:
  • The authors stated that outliers at some time points could hardly be explained and might be due to seasonal or other factors affecting regeneration intensity.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Visceral Pleura, Mesothelium, Epithelium, Fibroblast.

Related studies

• Experimentally induced mesothelioma in white rats in response to intraperitoneal administration of amorphous crocidolite asbestos: preliminary report — K. Kolev (1982)
• Pulmonary bombesin in experimentally induced asbestosis in rats — R. Day, I. Lemaire, et al. (1985)
• Characteristics of tumors and tumor cells cultured from experimental asbestos-induced mesotheliomas in rats — J.E. Craighead, N.J. Akley, et al. (1987)
• mRNA expression patterns in different stages of asbestos-induced carcinogenesis in rats — H. Sandhu, W. Dehnen, et al. (2000)
• DNA fingerprint analysis reveals differences in mutational patterns in experimentally induced rat peritoneal tumors, depending on the type of environmental mutagen — N. Kociok, K. Unfried, et al. (1999)
• Mass and number of fibres in the pathogenesis of asbestos-related lung disease in rats — J.M. Davis, S.T. Beckett, et al. (1978)

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