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

Our plain-English summary of 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, by M.L. Shin, H.I. Firminger (The American Journal of Pathology, 1973).

The study

• Authors: M.L. Shin, H.I. Firminger
• Journal: The American Journal of Pathology
• Published: 1973;70(3):291-313
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Malignant mesotheliomas were induced in the rat peritoneum by a single injection of chrysotile or crocidolite asbestos fibers. The immediate toxicity of the fibers was noted in both groups of animals, producing approximately 40% mortality, within 8 days after the injection associated with acute peritonities. Tissue reactions to these two types of asbestos were significantly different. Crocidolite fibers were easily seen by light microscopy, in the tissue sections throughout the period of study, and they produced foreign-body giant cell granulomas. However, giant cells were not seen in chrysotile granulomas, and the asbestos fibers were only seen by electron microscopic study. They appeared to be coated by a protein-like substance. During earlier stages of tumorigenesis, the epithelioid and/or mixed cell type mesotheliomas seemed to have no specific relationship to granulomas, but pure spindle cell tumors were seen to develop in close relationship to granulomas, and they appear to be fibrosarcomas. Electron microscopic and histochemical methods were used to define the morphologic characteristics of the tumor cells. The formation of hyaluronic acid was found in cells of the epithelioid type, contrasted with extracellular accumulation in the spindle cell tumors.

In plain English

In this animal experiment, 200 male Wistar rats each received a single injection into the abdominal cavity of 50 mg of asbestos. Half got chrysotile B, a Canadian UICC reference sample, and half got South African crocidolite. The experiment ended 14 months after injection. In the first 3 days 24 chrysotile and 29 crocidolite rats died, and 18 and 8 more died over the next 5 days, about 40% overall. The animals that died had acute peritonitis, which in most cases appeared free of bacterial infection. Crocidolite produced foreign-body giant cells in 48 of 63 surviving rats; none of the 58 surviving chrysotile rats showed them. The first mesothelioma appeared at 7 months. Among rats surviving 7 to 14 months, malignant peritoneal tumors developed in 9 of 45 crocidolite rats and 8 of 33 chrysotile rats (17 of 78 overall). Four rats, two per group, had reticulum cell sarcomas. The authors concluded that both fibers appeared carcinogenic for mesothelial cells and fibroblasts. They found no definitive evidence that tumors arose directly from granulomas, except 3 spindle cell tumors they considered fibrosarcomas.

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 (single intraperitoneal injection of asbestos in rats, followed for up to 14 months, with light and electron microscopy and histochemistry)
• Who was studied: 200 male Wistar rats weighing 150 to 180 g, studied at the Department of Pathology, University of Maryland School of Medicine, Baltimore; 100 per fiber group; dates of the experiment not stated
• Exposure: a single intraperitoneal injection of 50 mg of asbestos in 2 ml of saline: UICC standard reference chrysotile B (Canadian) in half the rats, UICC crocidolite (South African) in the other half
• Main results:
  • Early deaths: in the first 3 days, 24 chrysotile rats and 29 crocidolite rats died; over the next 5 days, 18 more chrysotile and 8 more crocidolite rats died. The authors described this as an overall 40% mortality in both groups by 8 days. Adding the article's counts gives 42 of 100 chrysotile rats and 37 of 100 crocidolite rats (a calculation, not a figure the article prints).
  • The animals that died early had acute peritonitis; most appeared to have aseptic (non-bacterial) peritonitis, as peritoneal cultures grew no bacteria
  • 121 rats survived (63 crocidolite, 58 chrysotile) and developed chronic inflammatory lesions
  • Crocidolite produced a foreign-body giant cell reaction in 48 of 63 surviving rats; no giant cells were seen in any of the 58 chrysotile rats
  • The first mesothelioma developed 7 months after injection
  • Malignant peritoneal tumors among rats surviving 7 to 14 months: crocidolite 9 of 45 (1 spindle cell, 4 epithelioid, 4 mixed); chrysotile 8 of 33 (2 spindle cell, 4 epithelioid, 2 mixed); total 17 of 78
  • Of the 78 rats studied from month 7 to 14, 21 (27%) developed malignant neoplasms; 17 were malignant peritoneal mesotheliomas (21.8%), more or less equally distributed between the two groups
  • The four non-mesothelial tumors, two in each group, were interpreted as reticulum cell sarcomas
  • Three epithelioid mesotheliomas spread to the lung, one of them also to a mesenteric lymph node; one mixed-type tumor spread to the lung
  • Hyaluronic acid was found inside epithelioid tumor cells; in spindle cell tumors it was found in the spaces between cells
  • When lesions were transplanted under the skin of other rats, only one tumor, an epithelioid mesothelioma, grew
• The authors' conclusion: The authors concluded that both chrysotile and crocidolite appear to have carcinogenic properties for mesothelial cells and for fibroblasts. In their view there was no definitive evidence that tumors arose directly from the granulomas, except 3 purely fibromatous sarcomas in areas of adhesions.
• Limitations the authors state:
  • The authors state that the development of the spindle cell tumors was less clear, because reactive fibroblasts were hard to tell apart from tumor cells
  • The authors state that telling tumor fibroblasts apart from reactive stromal cells was difficult

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: Mesothelioma, Malignant Mesothelioma, Peritoneum, Chrysotile, Crocidolite, Granuloma, Tumorigenesis, Epithelioid.

Related studies

• Tissue response to intraperitoneal asbestos with preliminary report of acute toxicity of heart-treated asbestos in mice — J. Jagatic, M.E. Rubnitz, et al. (1967)
• Ultrastructure of mesothelial regeneration after intraperitoneal injection of asbestos fibres on rat omentum — S. Gonzalez, J. Friemann, et al. (1991)
• Additional atypical malignant mesothelioma after intraperitoneal injection of mineral fibres in rats — K. Kamino, H. Ernst, et al. (1993)
• An assessment of the fibrogenic potential of two refractory fibres by intraperitoneal injection in rats — G.H. Pigott, J. Ishmael (1981)
• Epithelial outgrowths from lung tissue following intrapleural injection of asbestos dust in experimental animals — J.M. Davis (1971)
• Cellular reaction on the intraperitoneal injection of four types of polylactide particulates — A. van Sliedregt, M. Knook, et al. (1992)

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