Oxygen radicals and asbestos carcinogenesis

Our plain-English summary of Oxygen radicals and asbestos carcinogenesis, by V.D. Moyer, C.A. Cistulli, C.A. Vaslet, et al (Environmental Health Perspectives, 1994).

The study

• Authors: V.D. Moyer, C.A. Cistulli, C.A. Vaslet, A.B. Kane
• Journal: Environmental Health Perspectives
• Published: 1994;102 Suppl 10(Suppl 10):131-6
• Type of article: Review
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos fibers have been shown to generate reactive oxygen species using a variety of in vitro assays. It is hypothesized that these highly reactive metabolites mediate the development of malignant mesothelioma induced by asbestos fibers. DNA is a potential target of oxidant attack. Adaptive responses to oxidant injury have been described during exposure of mesothelial cells to asbestos fibers in vitro. Failure of these adaptive responses may lead to genetic instability and alterations in oncogenes and tumor suppressor genes that confer a proliferative advantage to emerging neoplastic mesothelial cells.

In plain English

This article was a review, presented at a 1993 conference, of laboratory evidence that reactive oxygen species (highly reactive forms of oxygen) produced by asbestos fibers may help cause malignant mesothelioma. Alongside other researchers' work, the authors described findings from their own laboratory using crocidolite asbestos in mice and in mouse mesothelial cells. They reported that crocidolite caused two kinds of chromosome damage in mouse mesothelial cells grown in the laboratory and increased hydrogen peroxide inside these cells. They also reported preliminary evidence that crocidolite raised levels of the p53 protein. Among 22 mouse mesothelial cell lines, one third of the tumor-forming lines showed reduced or absent expression of the p53 gene, and only 2 of 17 tumor-forming lines showed any mutant p53 protein. As a working hypothesis, the authors proposed that oxidants damage DNA, that cells at first adapt through p53, and that repeated damage to genes such as p53 leads to genetic instability and tumor growth. They noted that most of the evidence came from laboratory or short-term studies.

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: Review and conference paper proposing a hypothesis, including summaries of the authors' own laboratory experiments in mice and mouse mesothelial cell lines
• Who was studied: Mouse (murine) mesothelial cells grown in the laboratory, including 22 murine mesothelial cell lines, and mice given injections of asbestos into the abdominal cavity. No human subjects were studied by the authors.
• Exposure: UICC crocidolite asbestos fibers added to cell cultures at doses of 1 to 20 per square centimetre for 24 to 48 hours. The dose unit is garbled in the scan. Mice in the authors' model received single or repeated weekly injections of crocidolite into the abdominal cavity.
• Main results:
  • In mouse mesothelial cells, crocidolite fibers induced both kinds of micronucleus damage: the kind seen with chromosome-breaking agents and the kind seen with agents that change chromosome number.
  • Mouse mesothelial cells exposed to crocidolite in the laboratory showed increased hydrogen peroxide generated inside the cells.
  • The authors had preliminary evidence of increased p53 protein in response to crocidolite fibers.
  • Among the mouse mesothelial cell lines, one third of tumor-forming lines showed reduced or absent p53 gene expression, which correlated with partial deletions in exon 1. All of these lines came from mice with locally invasive tumors.
  • Only 2 of 17 tumor-forming cell lines showed any mutant p53 protein, in less than 2% of the cells. Another researcher (A. Pellicer, unpublished) found no point mutations in exons 5 through 9 of the p53 gene in these lines.
  • In the mouse injection model, coating fibers with deferoxamine or injecting catalase conjugated to polyethylene glycol was reported to decrease the acute toxicity of crocidolite.
• The authors' conclusion: The authors hypothesized that oxidants cause DNA breaks and trigger a growth-arrest pathway in mesothelial cells after acute asbestos exposure. They proposed that repeated exposures damage key genes such as p53, after which genetic changes accumulate and malignant mesothelioma can develop.
• Limitations the authors state:
  • Most of the evidence came from laboratory studies or short-term effects of asbestos, while mesotheliomas develop over decades in humans.
  • Most mesothelioma cell lines studied were derived from advanced tumors, so the stage at which the genetic changes appear is unknown.
  • The authors described the experimental studies as limited.

Topics

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

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Reactive Oxygen Species (ROS), Malignant Mesothelioma, Mesothelial Cells, Tumor Suppressor Gene.

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• Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis — V. Vallyathan, X. Shi, et al. (1998)
• The role of oxygen free radicals in occupational and environmental lung diseases — V. Vallyathan, X. Shi (1997)
• Oxygen radicals and asbestos-mediated disease — T.R. Quinlan, J.P. Marsh, et al. (1994)
• Involvement of protein kinase C, phospholipase C, and protein tyrosine kinase pathways in oxygen radical generation by asbestos-stimulated alveolar macrophage — Y. Lim, S.H. Kim, et al. (1997)

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