Mesotheliomas induced in rats by the fibrous mineral erionite are independent from p53 alterations

Our plain-English summary of Mesotheliomas induced in rats by the fibrous mineral erionite are independent from p53 alterations, by E.V. Kleymenova, G. Horesovsky, L.N. Pylev, et al (Cancer Letters, 1999).

The study

• Authors: E.V. Kleymenova, G. Horesovsky, L.N. Pylev, J. Everitt
• Journal: Cancer Letters
• Published: 1999;147(1-2):55-61
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The development of human malignant mesothelioma (MM) is strongly associated with occupational or environmental exposure to certain natural mineral fibers, although the genetic mechanisms underlying this malignancy remain unclear. Although the p53 gene is frequently mutated in various tumors, human asbestos-associated MMs appear to develop independently from p53 alterations. The high mesotheliomagenic potency of natural fibrous mineral erionite is well established in humans and rodents, but no data regarding genetic alterations in erionite-associated tumors are currently available. Previous speculations that the oncogenic mechanisms underlying asbestos and erionite carcinogenesis may differ led us to examine whether the p53 gene is targeted in erionite carcinogenesis. Fifteen erionite-induced rat MMs as well as six cell lines derived from asbestos-induced and spontaneous rat MM were analyzed for p53 mutations by direct DNA sequencing and immunohistochemical analysis. Both approaches did not reveal p53 alterations in rat MM samples used in the study indicating that, similar to asbestos carcinogenesis, erionite carcinogenesis does not target the p53 tumor suppressor gene.

In plain English

This was a laboratory study in rats. The authors injected 20 mg of erionite, a natural zeolite fiber from the Grusia Mines (former USSR), into the peritoneal (abdominal) cavity of each of 40 young male Wistar rats, three times at monthly intervals. Of the 40 rats, 39 developed peritoneal mesothelioma, 10 months to 1 year after the last injection. The authors examined 15 of these tumors for changes in p53, a gene often damaged in cancers. Ten were sequenced in the gene's core region (exons 5 to 8). All showed only the normal (wild-type) sequence, and the complete p53 coding sequence was obtained for only three. Ten were stained for p53 protein. None showed detectable build-up of the protein, which can signal p53 inactivation by mutation or by binding to other proteins. p53 was also sequenced in six rat mesothelioma cell lines: three from chrysotile-induced, two from crocidolite-induced and one from spontaneous tumors. No mutations were found. The authors concluded that, like asbestos, erionite causes these tumors without targeting p53. They wrote that staining many rat mesotheliomas induced by different mineral fibers was needed to clarify whether p53 build-up indicates p53 dysfunction in these tumors.

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 (rats injected with erionite), with genetic and protein analysis of the resulting tumors and of rat mesothelioma cell lines
• Who was studied: 40 young male Wistar rats. 15 of the resulting tumors were analyzed. Six rat mesothelioma cell lines were also analyzed: three from peritoneal mesothelioma induced by chrysotile asbestos, two from pleural mesothelioma induced by crocidolite asbestos, and one from a spontaneous mesothelioma of the tunica vaginalis testis.
• Exposure: Erionite from Grusia Mines (former USSR), 20 mg in sterile saline, injected into the peritoneal cavity three times at monthly intervals. The cell lines came from tumors induced by chrysotile or crocidolite asbestos, or from a spontaneous tumor.
• Main results:
  • 39 of the 40 erionite-injected rats developed peritoneal mesothelioma, 10 months to 1 year after the last injection
  • In the 10 erionite-induced tumors sequenced in the p53 core region (exons 5 to 8), only the normal (wild-type) sequence was found. The complete p53 coding sequence was obtained for three of them.
  • In the 10 erionite-induced tumors stained for p53 protein, no overexpression was found in tumor cells or in nearby abnormal mesothelial cells. Control rat nasal cancers known to carry mutant p53 did stain positive.
  • No p53 mutations were found by sequencing in the six rat mesothelioma cell lines (chrysotile-induced, crocidolite-induced and spontaneous)
• The authors' conclusion: The authors concluded that the absence of p53 changes in their erionite-induced rat mesotheliomas indicated that, as with asbestos, erionite carcinogenesis does not target the p53 tumor suppressor gene.
• Limitations the authors state:
  • The authors stated that p53 protein staining in a large number of rat mesotheliomas induced by different mineral fibers is needed to clarify whether p53 accumulation indicates p53 dysfunction in these tumors.

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, erionite, Environmental Exposure, Mineral Fiber, Carcinogenesis, Tumor Suppressor Gene.

Related studies

• New insights into the toxicity of mineral fibres: A combined in situ synchrotron μ-XRD and HR-TEM study of chrysotile, crocidolite, and erionite fibres found in the tissues of Sprague-Dawley rats — A.F. Gualtieri, N. Bursi Gandolfi, et al. (2017)
• Lung injury and expression of p53 and p16 in Wistar rats induced by respirable chrysotile fiber dust from four primary areas of China — Y. Zeng, Y. Cui, et al. (2018)
• Pluripotential nature of mesotheliomata induced by inhalation of erionite in rats — N.F. Johnson, R.E. Edwards, et al. (1984)
• Renal cell carcinoma development in the rat independent of alterations at the VHL gene locus — C. Walker, Y.T. Ahn, et al. (1996)
• Additional atypical malignant mesothelioma after intraperitoneal injection of mineral fibres in rats — K. Kamino, H. Ernst, et al. (1993)
• Prognostic significance of Bax and Fas ligand in erionite and asbestos induced Turkish malignant pleural mesothelioma — N. Kokturk, P. Firat, et al. (2005)

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