Cellular and molecular mechanisms of asbestos carcinogenicity: implications for biopersistence

Our plain-English summary of Cellular and molecular mechanisms of asbestos carcinogenicity: implications for biopersistence, by J.C. Barrett (Environmental Health Perspectives, 1994).

The study

• Author: J.C. Barrett
• Journal: Environmental Health Perspectives
• Published: 1994;102 Suppl 5(Suppl 5):19-23
• Type of article: Review
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Carcinogenic agents can influence the carcinogenic process either by mutating critical target genes or by increasing the number of cells at risk for mutations. Cytogenetic and molecular studies of asbestos-related cancers indicate that inactivation or loss of multiple tumor suppressor genes occurs during lung cancer development. Aneuploidy and other chromosomal changes induced by asbestos fibers may be involved in genetic alterations in asbestos-related cancers. Furthermore, asbestos fibers may influence the carcinogenic process by inducing cell proliferation, free radicals, or other promotional mechanisms. Therefore, asbestos fibers may act at multiple stages of the carcinogenic process by both genetic and epigenetic mechanisms. Biopersistence is undoubtedly important in fiber carcinogenicity. However, the time required for a fiber to remain in the lung to exert a cancer-related effect is difficult to specify.

In plain English

This article was a review, presented at a 1992 workshop in Lyon, France, on how long fibers persist in the body (biopersistence). It summarized earlier published laboratory and tumor studies on how asbestos and other mineral fibers might contribute to cancer, mainly mesothelioma. The review described reports of repeated, non-random chromosome changes in human mesotheliomas, involving chromosomes 1, 3, 5, 6 and 7 among others. One cited study found extra copies of part of chromosome 5 in 6 of 7 human mesothelioma cell lines. The author noted that no tumor suppressor gene or specific oncogene had yet been shown to have a direct role in mesothelioma. Cited cell studies indicated that asbestos fibers did not cause gene mutations but did cause chromosome changes, and that long, thin fibers were more active than short, thick ones. The author concluded that fibers may act at early or late stages of cancer development and that biopersistence is important. The author also concluded that the time a fiber must stay in the lung to have an effect is very difficult to determine, and that very short exposures may still be significant.

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: Narrative review of published cytogenetic, molecular and cell-culture studies, presented as a workshop paper (no new data reported)
• Who was studied: No study population of its own. The author reviewed published studies of chromosome changes in human mesotheliomas and mesothelioma cell lines, and laboratory studies of human and rodent cells exposed to asbestos.
• Exposure: Asbestos and other mineral fibers in general. Cited cell-culture studies used crocidolite and chrysotile asbestos.
• Main results:
  • The review reported that published studies found recurring chromosome changes in human mesotheliomas, including deletions or rearrangements of chromosome 1. One cited group reported these at a frequency above 60%.
  • One cited study (Pelin-Enlund and coworkers) reported an excess of the short arm of chromosome 5 in 6 out of 7 human mesothelioma cell lines.
  • The author stated that a specific oncogene involved in mesotheliomas had not yet been identified, and that a direct role for any tumor suppressor gene had yet to be demonstrated.
  • The author stated that asbestos and other mineral fibers do not induce gene mutations but are active as chromosomal mutagens.
  • According to cited cell studies, asbestos-induced cell transformation depended on fiber size, with long, thin fibers more active than short, thick fibers.
  • The author proposed that fibers may also promote cancer by stimulating cell proliferation, either after cell injury or through inflammatory cells releasing cytokines and growth factors.
• The authors' conclusion: The author concluded that asbestos fibers could influence cancer development at early or late stages through both genetic and epigenetic mechanisms. In the author's view, biopersistence is important, but the degree of biopersistence needed for fiber carcinogenicity is very difficult to determine. Longer exposures increase the probability of a cancer response, but very short exposures may still be significant.

Topics

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

Medical terms in this study, explained in our Lexicon: biopersistence, Carcinogenic, Tumor Suppressor Gene, Lung Cancer.

Related studies

• Possible cellular and molecular mechanisms for asbestos carcinogenicity — C. Walker, J. Everitt, et al. (1992)
• Cellular and molecular mechanisms of asbestos-induced fibrosis — R. Robledo, B. Mossman (1999)
• Cellular and molecular mechanisms of asbestosis — B.T. Mossman, R. Gilbert, et al. (1986)
• Molecular and Cellular Mechanism of Action of Chrysotile Asbestos in MRC5 Cell Line — A. Kussainova, O. Bulgakova, et al. (2023)
• Role of mutagenicity in asbestos fiber-induced carcinogenicity and other diseases — S.X. Huang, M.C. Jaurand, et al. (2011)
• Ascorbic acid modifies the surface of asbestos: possible implications in the molecular mechanisms of toxicity — G. Martra, M. Tomatis, et al. (2003)

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