Analysis of K-ras and p53 mutations in mesotheliomas from humans and rats exposed to asbestos

Our plain-English summary of Analysis of K-ras and p53 mutations in mesotheliomas from humans and rats exposed to asbestos, by Z. Ni, Y. Liu, N. Keshava, et al (Mutation Research, 2000).

The study

• Authors: Z. Ni, Y. Liu, N. Keshava, G. Zhou, W. Whong, T. Ong
• Journal: Mutation Research
• Published: 2000;468(1):87-92
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma is known to be associated with asbestos exposure. However, the mechanism of mesothelial carcinogenesis in relation to the activation of proto-oncogenes or inactivation of tumor suppressor genes remains unclear. In this study, the PCR-Primer Introduced Restriction Site (PCR-PIRS) assay was employed to examine mutations in the K-ras proto-oncogene in mesothelioma tissues from workers exposed to asbestos and from rats treated with asbestos. Mutations in exons 5-8 of the p53 tumor suppressor gene were determined by direct DNA sequence analysis. Results of the PCR-PIRS analysis revealed no mutations in codons 12, 13 or 61 of the K-ras gene in any of the 17 human or 22 rat mesothelioma tissue samples. These results were confirmed by direct DNA sequence analysis. No mutations were found in exons 5-8 of the p53 gene in any of the mesothelioma tissue samples analyzed. These results and the results reported by others indicate that the K-ras proto-oncogene and p53 tumor suppressor gene may not play a critical role in the induction of mesothelioma by asbestos either in humans or in rats.

In plain English

This laboratory study looked for gene changes (mutations) in two genes, K-ras and p53, in mesothelioma tumor tissue. The human samples were autopsy tissue from 17 workers exposed to asbestos, collected at the hospital of West China University of Medical Sciences. The article does not describe the workers' jobs or fiber types. In the animal experiment, 60 Wistar rats (30 males and 30 females) were injected twice, one month apart, with crocidolite fibers. Of these, 22 developed tumors after 1 to 1.5 years, which microscope examination showed were malignant mesotheliomas, and only these 22 rats' tumors were analyzed. The researchers found no mutations at codons 12, 13 or 61 of the K-ras gene in any of the 17 human or 22 rat tumors, and direct DNA sequencing confirmed this. They also found no mutations in exons 5 to 8 of the p53 gene in any of these samples. Together with other published studies, the authors concluded that mutations in K-ras and p53 may not play a crucial role in mesothelioma development in humans or rats.

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: Laboratory study analyzing gene mutations in stored human tumor tissue and in tumors induced in rats (animal experiment)
• Who was studied: Mesothelioma autopsy samples from 17 asbestos-exposed workers, collected at the hospital of West China University of Medical Sciences, China, plus mesothelioma tissue from the 22 of 60 crocidolite-injected rats that developed tumors
• Exposure: Humans: occupational asbestos exposure, with no fiber type or job details given. Rats: 60 Wistar rats (30 males, 30 females) injected twice, one month apart, with crocidolite fibers. The dose and fiber-size units are garbled in the scanned text.
• Main results:
  • 22 of the 60 rats exposed to crocidolite developed tumors, with latency of 1 to 1.5 years. On histological examination the tumors were malignant mesotheliomas.
  • No mutations at codons 12, 13 or 61 of the K-ras gene in any of the 17 human or 22 rat mesothelioma tissues (PCR-PIRS assay)
  • Direct DNA sequencing confirmed the absence of K-ras mutations in both the human and the rat tissues
  • No mutations in exons 5 to 8 of the p53 gene in any of the 17 human or 22 rat mesothelioma samples
• The authors' conclusion: The authors concluded that, together with other published results, their findings suggest that mutations in K-ras and p53 may not play a crucial role in mesothelioma development in humans or in rats

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Asbestos Exposure, Carcinogenesis, Tumor Suppressor Gene.

Related studies

• P53 mutations in tumours induced by intraperitoneal injection of crocidolite asbestos and benzo[a]pyrene in rats — K. Unfried, N. Kociok, et al. (1997)
• p53 and ras gene mutations in lung cancer: implications for smoking and occupational exposures — K. Husgafvel-Pursiainen, M. Ridanpää, et al. (1995)
• Lung cancer and past occupational exposure to asbestos. Role of p53 and K-ras mutations — K. Husgafvel-Pursiainen, A. Karjalainen, et al. (1999)
• K-ras mutations in human adenocarcinoma of the lung: association with smoking and occupational exposure to asbestos — K. Husgafvel-Pursiainen, P. Hackman, et al. (1993)
• Crocidolite induces cell transformation and p53 gene mutation in BALB/c-3T3 cells — F. Lin, Y. Liu, et al. (2000)
• mRNA expression patterns in different stages of asbestos-induced carcinogenesis in rats — H. Sandhu, W. Dehnen, et al. (2000)

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