Establishment of a murine model of malignant mesothelioma

Our plain-English summary of Establishment of a murine model of malignant mesothelioma, by M.R. Davis, L.S. Manning, D. Whitaker, et al (International Journal of Cancer, 1992).

The study

• Authors: M.R. Davis, L.S. Manning, D. Whitaker, M.J. Garlepp, B.W. Robinson
• Journal: International Journal of Cancer
• Published: 1992;52(6):881-6
• Cited by: 163 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with previous asbestos exposure and is generally found to be resistant to conventional forms of therapy. Adequate scientific and clinical assessment of this disease has been severely limited by the relatively low incidence of mesothelioma and the lack of representative cell lines and animal models. The purpose of this study was to develop an asbestos-induced murine model of MM both as an in vivo-passaged malignancy and as in vitro-established cell lines. Such a model system would be invaluable for use in the study of various cellular, molecular and genetic aspects of the disease, and for the pre-clinical evaluation of potential therapeutic agents. BALB/c and CBA mice were injected intraperitoneally with crocidolite asbestos. Seven to 25 months after exposure, 35% of the mice developed mesothelioma (5 BALB/c, 9 CBA), as determined by standard cytological and histological parameters. From these primary tumours, 12 continuously growing cell lines (5 BALB/c, 7 CBA) were established in culture. All have been confirmed as mesothelioma by cytological and ultrastructural (electron microscopy) analyses. These lines have been in culture for 7 to 24 months and have achieved passages above 32 (range 32 to 106). As in the human disease, the murine mesothelioma lines vary in their morphology and growth rates (doubling times ranging from 14 to 30 hr). All cell lines produced tumours when injected into syngeneic mice.

In plain English

This was an animal experiment by researchers in Western Australia that aimed to create a mouse model of malignant mesothelioma. Twenty BALB/c and 20 CBA female mice were each injected into the abdominal cavity with 2.5 mg of Wittenoom Gorge crocidolite asbestos. Mesothelioma developed 7 to 25 months later in 14 mice: 9 of 20 CBA mice (45%) and 5 of 20 BALB/c mice (25%). The authors reported this difference as statistically significant (p less than 0.05). All 14 mice had blood-stained fluid in the abdomen, some had solid tumours in the peritoneal cavity, and none showed spread to other organs. No cancer was found in the other 26 mice. Twelve of the 14 tumours were grown continuously in the laboratory as cell lines, which varied in shape and growth rate. All 12 lines produced tumours when injected into mice of the same strain, although two lines were tested only in preliminary studies. The authors concluded that the mouse tumour mimics the human tumour in most respects.

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: mice were injected with asbestos to induce mesothelioma, and the resulting tumours were grown as laboratory cell lines
• Who was studied: 40 female mice aged 6 to 8 weeks (20 BALB/c and 20 CBA) from the Animal Resource Centre in Perth, Western Australia, followed for up to 28 months
• Exposure: A single injection into the peritoneal (abdominal) cavity of 2.5 mg of crocidolite asbestos from a reference sample of Wittenoom Gorge crocidolite
• Main results:
  • Mesothelioma developed in 9 of 20 CBA mice (45%) and 5 of 20 BALB/c mice (25%). The authors reported the difference as significant (p less than 0.05).
  • Tumours developed between 7 and 25 months after the asbestos injection
  • All 14 tumour-bearing mice had blood-stained ascites (abdominal fluid), and some had solid tumours within the peritoneal cavity
  • No metastasis (spread to other organs) was found in any of the tumour-bearing mice
  • No malignancy was identified in the remaining 26 mice
  • 12 of the 14 mesotheliomas were established as continuous cell lines in culture, reaching 32 to 106 passages
  • Growth rates of the cell lines varied. The results section gives doubling times from 16 hours (line AC16) to 30 hours.
  • All cultured cell lines produced tumours when injected into mice of the same strain. Lines AC14 and AC32 were not tested in the main series of experiments and produced tumours only in preliminary studies.
  • Lines AB1 and AC29 were the most tumour-forming, producing gross ascites 27 and 24 days respectively after injection into the abdomen
• The authors' conclusion: The authors concluded that this mouse tumour mimics the human tumour in most respects and could be used to study the biology and immunobiology of mesothelioma
• Limitations the authors state:
  • Antisera used to characterise human mesothelioma could not be used in mice because of species differences, so the authors relied on electron microscopy to characterise each cell line

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Wittenoom, Western Australia

All asbestos mines

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Asbestos Exposure, Mesothelioma, Crocidolite.

Related studies

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• Potential for interferon-alpha-based therapy in mesothelioma: assessment in a murine model — H. Bielefeldt-Ohmann, D.R. Fitzpatrick, et al. (1995)
• A murine model of asbestosis — B.E. Bozelka, P. Sestini, et al. (1983)
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• Efficacy of repeated adenoviral suicide gene therapy in a localized murine tumor model — E.S. Lambright, S.D. Force, et al. (2000)
• Establishment of a cell line from a Japanese patient useful for generating an in vivo model of malignant pleural mesothelioma — A. Sato, I. Torii, et al. (2011)

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