Asbestos fibers are mutagenic after all: new signs of orthodoxy for a paradoxical group of carcinogens

Our plain-English summary of Asbestos fibers are mutagenic after all: new signs of orthodoxy for a paradoxical group of carcinogens, by T.M. Fasy (Annals of the New York Academy of Sciences, 1991).

The study

• Author: T.M. Fasy
• Journal: Annals of the New York Academy of Sciences
• Published: 1991;643:271-9
• Type of article: Review
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this review, the author examined whether asbestos fibers can damage DNA and cause mutations, at a time when the prevailing view held that they lacked clear genotoxic potential. He summarized earlier work. There was general agreement that asbestos fibers induced aneuploidy and chromosome breaks. Results on sister chromatid exchanges disagreed. Mammalian cell specific-locus assays had reported little or no mutagenic activity. The author argued that, because a mutation is a heritable change in the genome, aneuploidy counts as mutation, so asbestos fibers should be regarded as mutagens. He contended that the standard specific-locus assays cannot detect large multilocus deletions, because cells that lose neighbouring essential genes do not survive. He outlined possible routes to gene mutation: fibers adhering to, entangling or piercing chromosomes; generation of reactive oxygen species; and chrysotile-mediated uptake and insertion of foreign DNA. He described two newer assays able to detect large deletions, AS52 and AL-J1. He cited an early unpublished report by Waldren that chrysotile caused loss of a marker, and later reports that UICC chrysotile and crocidolite were highly mutagenic in the AL-J1 system. He then discussed how deletion mutations could inactivate tumor-suppressor genes, and argued that asbestos may also act as a tumor promoter. He rejected the view that only initiators are genotoxic as a false dichotomy. He concluded that asbestos oncogenesis may serve as a clarifying model rather than an inexplicable exception.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This article was a review and commentary by one author from the Department of Pathology, Mount Sinai School of Medicine, New York, on whether asbestos fibers cause mutations. It reported no new experiments of its own. The author argued that asbestos fibers should be regarded as mutagens because they induce aneuploidy, the loss or gain of whole chromosomes. The author also argued that the standard tests in cultured mammalian cells, which had mostly found little or no mutation from asbestos, cannot detect very large deletion mutations, because cells that lose nearby essential genes die. The article described two newer tests based on Chinese hamster ovary cells (AS52 and AL-J1) that can detect such deletions. It noted that other researchers had reported reference samples of Rhodesian chrysotile and crocidolite to be highly mutagenic in the AL-J1 test, and that work on chrysotile, amosite and crocidolite in AS52 cells was under way. The author proposed that asbestos-caused deletions could inactivate tumor-suppressor genes and that asbestos may also act as a tumor promoter.

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 commentary (no new experimental data reported)
• Who was studied: No people or animals were studied. The article discussed published laboratory studies of asbestos in cultured mammalian cells, including Chinese hamster ovary cell mutation assays.
• Exposure: Asbestos fibers in cell-culture studies: chrysotile and crocidolite, and UICC reference samples of Rhodesian chrysotile, crocidolite, Canadian chrysotile and amosite
• Main results:
  • The author argued that asbestos fibers should be regarded as mutagens because they efficiently induce aneuploidy (whole-chromosome changes).
  • The author argued that the commonly used mammalian cell specific-locus assays are effectively blind to very large deletion mutations. Cells carrying such deletions die because essential genes near the target gene are lost with it.
  • The article described two newer assays able to detect large deletions, AS52 and AL-J1, both based on modified Chinese hamster ovary cells.
  • The article reported that other researchers (Hei, Waldren and coworkers) had found UICC reference samples of Rhodesian chrysotile and of crocidolite each highly mutagenic in the AL-J1 assay.
  • The article stated that Stankowski and coworkers were carrying out an assessment of UICC Canadian chrysotile, amosite and crocidolite in the AS52 assay.
  • The author listed possible ways asbestos might cause gene mutations. Fibers have been seen adhering to, entangling, severing or piercing chromosomes. Fibers can form reactive oxygen species. Chrysotile can act as a transfection agent that carries DNA into cells.
  • The author proposed that the ability of asbestos fibers to cause large deletion mutations, which can inactivate tumor-suppressor genes, may be linked to their ability to induce tumors and to increase the activity of other carcinogens.
  • The author rejected the view that only initiators are genotoxic and promoters never are. The author suggested asbestos fibers may act as tumor promoters through their toxicity to cells and their production of reactive oxygen species.
• The authors' conclusion: The author concluded that asbestos-caused cancer may serve as a clarifying model for understanding carcinogenesis, rather than an inexplicable exception to the rule.

Topics

Medical terms in this study, explained in our Lexicon: Reactive Oxygen Species (ROS), Chrysotile, UICC, Crocidolite, Carcinogenesis.

Related studies

• The genetic toxicity of human carcinogens and its implications — M.D. Shelby (1988)
• Absence of mutagenic activity of three forms of asbestos in liver epithelial cells — B. Reiss, S. Solomon, et al. (1982)
• Oxygen radical-mediated mutagenic effect of asbestos on human lymphocytes: suppression by oxygen radical scavengers — L.G. Korkina, A.D. Durnev, et al. (1992)
• The role of genotoxicity in asbestos-induced mesothelioma: an explanation for the differences in carcinogenic potential among fiber types — C.A. Barlow, L. Lievense, et al. (2013)
• Induction of metaphase and anaphase/telophase abnormalities by asbestos fibers in rat pleural mesothelial cells in vitro — M. Yegles, L. Saint-Etienne, et al. (1993)
• A study of the effect of chrysotile fiber surface composition on genotoxicity in vitro — M.J. Keane, J.W. Stephens, et al. (1999)

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