Mesothelial proliferation due to asbestos and man-made fibres. Experimental studies on rat omentum

Our plain-English summary of Mesothelial proliferation due to asbestos and man-made fibres. Experimental studies on rat omentum, by J. Friemann, K.M. Müller, F. Pott (Pathology, Research and Practice, 1990).

The study

• Authors: J. Friemann, K.M. Müller, F. Pott
• Journal: Pathology, Research and Practice
• Published: 1990;186(1):117-23
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 003679).

Abstract

The intraperitoneal test in rats has proven to be an appropriate method controlling fibrogenicity and carcinogenicity of asbestos fibres and other fibrous dusts. We analyzed the reaction patterns of mesothelial cover layer to different natural mineral fibres (crocidolite, chrysotile, actinolite, erionite, wollastonite) and man-made mineral and synthetic fibres (glass fibres 104/475, polypropylene, aramide fibres). The injection of doses between 0.01 and 100 mg dust suspended in saline solution led to a continued repairing proliferation of submesothelial connective tissue cells and focal submesothelial fibrosis. These changes were never observed after application of granular dusts as mine dust and quartz. After 15 to 28 months we often found an association of fibrosis and local reactive hyperplasia of partly atypical proliferation of rat omentum mesothelium. These changes were also demonstrated in cases without macroscopically visible tumors. In later stages the underlying fibrosis was often infiltrated and dissolved by mesotheliomas.

In plain English

In this animal experiment, the authors examined under a light microscope the omentum (a fatty fold of abdominal tissue) of rats injected in the abdominal cavity with fibres. One part used 64 female Sprague-Dawley rats killed 8 hours to 15 months after injection of crocidolite or chrysotile B. Another part used samples from earlier long-term studies in female Wistar rats given chrysotile, actinolite, erionite, wollastonite, glass, polypropylene or aramid (Kevlar) fibres, with quartz and saline as controls. Seven days after crocidolite injection, the lining cells (mesothelium) had grown and scarring had formed beneath them, and these changes continued throughout the study. Fifteen months after 1, 5 or 15 mg chrysotile, these changes were less intense than with crocidolite. Mild changes appeared even at very low chrysotile or actinolite doses where no fibres were visible, but never with quartz. Early mesotheliomas were found in 3 actinolite and 2 glass fibre cases. The authors concluded that, in these tests, tumour-causing potency depended far more on time of action, durability, size and length-to-width ratio than on physico-chemical properties, unless those affected durability. They noted that only a few samples were taken from each omentum.

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: light-microscopic examination of rat omentum after intraperitoneal (abdominal cavity) injection of fibres, including specimens from earlier long-term carcinogenicity studies
• Who was studied: 64 female Sprague-Dawley rats killed 8 hours to 15 months after injection. The study also used omentum specimens from long-term carcinogenicity studies in female Wistar rats. Those rats were killed in poor health no earlier than two years after injection and had no tumour visible to the naked eye in the abdominal cavity. Germany (Bochum and Düsseldorf).
• Exposure: Intraperitoneal injection, in saline, of the natural mineral fibres crocidolite (South Africa), chrysotile B (Canada), actinolite, erionite (Oregon) and wollastonite (India). Man-made and synthetic fibres were glass fibres JM 104/475, polypropylene and aramid (Kevlar). Crocidolite and chrysotile were given at 1, 5 or 15 mg in the first part; other doses ranged from 0.01 to 100 mg. Quartz and 1 ml 0.9% saline served as controls.
• Main results:
  • In crocidolite-injected rats, mesothelial proliferation and early submesothelial fibrosis were present 7 days after injection, even where there was no contact with the crocidolite granulomas.
  • In crocidolite-injected rats, these changes were interpreted as a repair process and continued for the whole study period.
  • Six months after injection, dense submesothelial fibrosis was seen only at the edges of some crocidolite-containing foreign-body granulomas. The authors suggested these areas could be precursors of sarcomatous transformation. In two animals, such findings occurred 15 months after injection, when the tumour had already spread into the adjacent pancreas.
  • Fifteen months after injection of 1, 5 or 15 mg chrysotile, submesothelial fibrosis and mesothelial proliferation were less intense than with crocidolite.
  • The same pattern appeared at much lower intensity after far lower doses (for example 0.05 mg chrysotile B or 0.01 to 0.25 mg actinolite). At these low doses, fibres could not be detected by light microscopy.
  • In the long-term study specimens, even very low doses were often associated with mild submesothelial fibrosis combined with mesothelial proliferation.
  • In the long-term specimens, early mesotheliomas were found in 3 actinolite cases and 2 glass fibre cases.
  • One of two omentums examined 27 months after injection of 5 x 4 mg aramid fibres (Kevlar) was infiltrated by an advanced epithelial mesothelioma.
  • In later stages, the underlying fibrosis was often infiltrated and dissolved by mesotheliomas.
  • These fibrosis and proliferation changes were never observed after intraperitoneal injection of quartz.
• The authors' conclusion: The authors concluded that their observations imply that the cancer-causing potency of mineral fibres in serosal tests is influenced far more by the time of action, durability, size and aspect ratio of the fibres than by physico-chemical properties, unless those properties matter for fibre durability. They also regarded the activation of submesothelial tissue as a rather unspecific response to injury of the mesothelium by fibrous dusts that are long and fine enough.
• Limitations the authors state:
  • Only a few specimens were processed from each omentum in the long-term studies, so the authors could make no general judgement about the absolute or relative effectiveness of the dusts in each animal.
  • The authors could not rule out that some of the sarcomas or mesotheliomas seen were the kind that occur without any treatment in up to about 5% of this species.
  • The starting point of the mesothelioma in the Kevlar-treated animal could not be determined exactly.

Topics

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

Medical terms in this study, explained in our Lexicon: Omentum, Crocidolite, Chrysotile, Actinolite, erionite, Wollastonite, Fibrosis, Mesothelium.

Related studies

• Ultrastructure of mesothelial regeneration after intraperitoneal injection of asbestos fibres on rat omentum — S. Gonzalez, J. Friemann, et al. (1991)
• Neoplastic and inflammatory processes of the peritoneum, omentum, and mesentery: diagnosis with CT — J.E. Hamrick-Turner, M.V. Chiechi, et al. (1992)
• Asbestos in extrapulmonary sites: omentum and mesentery — R.F. Dodson, M.F. O'Sullivan, et al. (2000)
• Combined adenomatoid tumor and well differentiated papillary mesothelioma of the omentum — Y. Hatano, Y. Hirose, et al. (2011)
• Gray scale sonographic presentation of a mesothelioma of the greater omentum — J.M. Shah, D.L. King (1979)
• Primary malignant mesothelioma of the greater omentum: report of a case — Y.C. Liu, Y.L. Kuo, et al. (2004)

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