Effects of Crocidolite Fibers on the Peritoneal Mesothelium of Rats

Our plain-English summary of Effects of Crocidolite Fibers on the Peritoneal Mesothelium of Rats, by K. Unfried, H. Sandhu, C. Schürkes, et al (Inhalation Toxicology, 2000).

The study

• Authors: K. Unfried, H. Sandhu, C. Schürkes, C. Albrecht, J. Abel
• Journal: Inhalation Toxicology
• Published: 2000;12 Suppl 3:149-55
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The assay of intraperitoneal (ip) injection to rats was used as experimental system to study the mechanisms of carcinogenic effects of fibrous dusts. With this test system, fibers were shown to induce mesothelioma in the peritoneal cavity. Although the data of the ip assay are discussed controversially in terms of risk assessment, it is a valuable tool to investigate the molecular mechanisms of mesothelioma carcinogenesis in vivo. This test system allows one to investigate both the effects of fibers on signal transduction and the genotoxic potential of fibers. On the level of mRNA expression, different stages of fiber-induced tumor development in the peritoneal space were examined using differential display techniques. Genes of signal transduction pathways are mainly affected by the fiber treatment; for example, the activation of genes for the AP-1 transcription factor could be observed in the tissues of the peritoneal cavity. Thus, our in vivo data confirm the findings reported from cell culture systems. Moreover, our results from the differential display assays reveal that genes involved in the integrin-linked signal transduction are upregulated. In addition, the ip assay can be applied to transgenic animals to perform mutagenicity testing. Using the Big Blue transgenic animal system, we provide data of a significant increase in mutation frequency after treatment with crocidolite asbestos.

In plain English

This laboratory study in rats and cultured cells, from a group in Düsseldorf, Germany, examined how crocidolite asbestos affects the mesothelium lining the abdominal (peritoneal) cavity. Rats received a single abdominal injection of crocidolite. The number of animals is not given. Compared with tissue from untreated rats, mesothelioma tumors and non-tumor fiber-treated tissue showed increased activity of several genes. These included c-myc, egf-r, genes for the AP-1 transcription factor, and genes for osteopontin, zyxin and integrin-linked kinase. In cultured cells, crocidolite and the man-made mineral fiber MMVF-21 switched on the protein Fra-1, while non-fibrous titanium dioxide did not. In specially bred Big Blue rats given 2 mg or 5 mg of UICC crocidolite, mutation frequencies were significantly increased at 12 and 24 weeks compared with spontaneous rates. G to T transversion was the most common mutation type. The authors concluded that this injection system can be used to study both gene-activity changes and the genotoxicity of asbestos. They noted that the gene changes might be triggered by other cell types involved in inflammation or fibrosis.

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 (intraperitoneal injection in rats, including Big Blue transgenic rats), with supporting in vitro cell culture experiments
• Who was studied: Rats given intraperitoneal injections, with the greater omentum examined; Big Blue transgenic rats for mutation testing; cultured RPM cells for in vitro work. The study was done at Heinrich Heine University, Düsseldorf, Germany. Numbers of animals are not given.
• Exposure: Single intraperitoneal injection of 2 mg South African crocidolite (gene expression studies), and of 2 mg or 5 mg UICC crocidolite in Big Blue rats (mutation studies). Salt solution (NaCl) was the negative control and benzo[a]pyrene the positive control. In vitro comparisons used crocidolite, MMVF-21 man-made mineral fiber and granular titanium dioxide.
• Main results:
  • In rat omentum tissue, genes for c-myc, egf-r and the AP-1 transcription factor showed enhanced expression at different stages of carcinogenesis.
  • Genes for osteopontin, zyxin and integrin-linked kinase were upregulated in response to asbestos treatment.
  • All genes identified also showed enhanced expression in cultured mesothelial or mesothelioma cells.
  • In cultured cells, UICC crocidolite and MMVF-21 induced Fra-1 protein expression. Granular titanium dioxide did not.
  • In Big Blue rats treated with crocidolite, mutation frequencies in the greater omentum were significantly increased at 12 and 24 weeks compared with spontaneous mutation rates. No numbers are given in the text.
  • G to T transversion was the most common mutation type in DNA from asbestos-treated animals.
• The authors' conclusion: The authors concluded that peritoneal administration of asbestos in rats makes it possible to study mRNA changes in signal transduction pathways as well as the genotoxicity of asbestos. They suggested that the mutations seem to be induced directly or indirectly by crocidolite fibers through reactive oxygen species.
• Limitations the authors state:
  • The authors could not rule out that the increased gene expression seen in animals was triggered by other cell types involved in inflammation or fibrosis.
  • The authors note that intraperitoneal injection data are disputed for risk assessment purposes.

Topics

Medical terms in this study, explained in our Lexicon: Crocidolite, Mesothelium, Carcinogenic, Mesothelioma, Peritoneal Cavity, Carcinogenesis.

Related studies

• Induction of 8-hydroxydeoxyguanosine by man made vitreous fibres and crocidolite asbestos administered intraperitoneally in rats — C. Schürkes, W. Brock, et al. (2004)
• Clearance and dimensional changes of crocidolite asbestos fibers isolated from lungs of rats following short-term exposure — V.L. Roggli, M.H. George, et al. (1987)
• Asbestos body formation and iron accumulation in mouse peritoneal granulomas after the introduction of crocidolite asbestos fibers — H.K. Koerten, J. Hazekamp, et al. (1990)
• P53 mutations in tumours induced by intraperitoneal injection of crocidolite asbestos and benzo[a]pyrene in rats — K. Unfried, N. Kociok, et al. (1997)
• PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma — D.B. Chapel, A.N. Husain, et al. (2017)
• Factors secreted by peritoneal macrophages are cytotoxic for transformed rat pleural mesothelium and mesothelioma cells — I.V. Kravchenko, V.A. Furalyov, et al. (2003)

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