Cellular defense mechanisms against asbestos fibers

Our plain-English summary of Cellular defense mechanisms against asbestos fibers, by C.A. Barlow, B.T. Mossman (Frontiers in Public Health, 2025).

The study

• Authors: C.A. Barlow, B.T. Mossman
• Journal: Frontiers in Public Health
• Published: 2025;13:1566473
• Type of article: Review
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Although inhalation of sufficient doses and dimensions of airborne asbestos dusts in an occupational setting can produce cancer in the lungs, pleura and peritoneum, tumors occur in <5-10% of exposed individuals, even among persons with considerable historical exposures. In this perspective, we review cell defense mechanisms that are involved in protective and adaptive responses to asbestos exposure. These adaptive responses are orchestrated through a multifaceted cellular program involving the concerted action of diverse stress response pathways, including antioxidant responses, DNA repair mechanisms, molecular mechanisms for intracellular signaling leading to proliferation, apoptosis, and inflammation, and cell cycle regulation. These cell defenses suggest that humans can adjust to moderate levels of stress or change without experiencing negative effects, implying the existence of a threshold dose. Likewise, reported no-observed adverse-effect levels (NOAELs) for various asbestos fiber types and asbestos-related cancers in experimental and epidemiological data further support the existence of a threshold dose and are discussed here.

Copyright © 2025 Barlow and Mossman.

In plain English

This article was a review, called a perspective by the authors, of how cells defend themselves against asbestos fibers and of evidence for a threshold dose. It reported no new experiments or new data on people. The authors described laboratory and animal studies of DNA repair, antioxidant responses, cell signaling, inflammation and DNA methylation. They summarized that oxidative stress could be counteracted by antioxidant responses at low asbestos concentrations. They cited one study that found no increase in pleural mesothelioma rates among women in urban compared with rural U.S. areas from 1973 to 2012. They also cited an analysis by Beckett and colleagues that gave chrysotile no-observed-adverse-effect levels for cumulative exposure of 97–175 f/cc-yr for lung cancer and 250–379 f/cc-yr for mesothelioma. Using published relative potency factors for mesothelioma, that analysis derived best-estimate mesothelioma levels of 2–5 f/cc-yr for predominately amosite-exposed populations and 0.6–1 f/cc-yr for predominately crocidolite-exposed populations. The authors noted that many of the studies they described lacked dose-response experiments and negative controls, and that most animal studies compared fibers by weight. The authors concluded that the literature strongly suggests thresholds for mesotheliomas and lung cancers promoted by asbestos.

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 (described by the authors as a perspective) of laboratory, animal and epidemiological literature; no new data
• Who was studied: No study population of its own; the authors reviewed published in vitro (cell and organ culture), animal and human epidemiological studies
• Exposure: Asbestos fibers, mainly the commercial types chrysotile, amosite and crocidolite
• Main results:
  • In summarizing the cell studies, the authors stated that oxidative stress in immune cells and target cells can be counteracted by antioxidant responses at low asbestos concentrations, and that these responses are overwhelmed at high fiber concentrations
  • A cited study in human bronchial epithelial cells (not this review's own work) found global DNA methylation after crocidolite or amosite but not after chrysotile, with no significant changes at the lowest amphibole concentrations
  • A cited study by Glynn et al. found no increase in pleural mesothelioma incidence rates among females in urban versus rural U.S. areas between 1973 and 2012, despite measured differences of up to 10-fold or more in ambient airborne asbestos concentrations
  • A cited analysis by Beckett et al., discussed in the context of predominately chrysotile-exposed cohorts, reported lower- and upper-bound chrysotile no-observed-adverse-effect levels (NOAELs) for cumulative exposure of 97–175 f/cc-yr for lung cancer and 250–379 f/cc-yr for mesothelioma
  • Beckett et al. applied published relative potency factors for mesothelioma to the chrysotile mesothelioma NOAEL. From this they derived best-estimate mesothelioma NOAELs of 2–5 f/cc-yr for predominately amosite-exposed populations and 0.6–1 f/cc-yr for predominately crocidolite-exposed populations
• The authors' conclusion: The authors concluded that their information and a review of the animal and human literature strongly suggest that thresholds exist for mesotheliomas and lung cancers promoted by asbestos, and that asbestos type matters in calculating NOAELs
• Limitations the authors state:
  • Many of the studies described lacked dose-response experiments and did not include non-disease-causing particles or fibers as negative controls
  • Most animal studies compared asbestos effects on an equal mass or weight basis, which makes comparison between experiments and with human exposure difficult
  • Laboratory and animal studies do not give precise estimates of the biologically effective dose under realistic human exposure conditions

Topics

Medical terms in this study, explained in our Lexicon: Pleura, Peritoneum, Asbestos Exposure, Apoptosis, Inflammation, NOAEL.

Related studies

• Repression of GADD153/CHOP by NF-kappaB: a possible cellular defense against endoplasmic reticulum stress-induced cell death — S. Nozaki, G.W. Sledge, et al. (2001)
• Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1 — C. Loreto, R. Caltabiano, et al. (2020)
• Antioxidant defense mechanisms and the toxicity of fibrous and nonfibrous particles — K.E. Driscoll, J.M. Carter, et al. (2002)
• Antioxidant defense mechanisms of human mesothelioma and lung adenocarcinoma cells — K. Järvinen, P. Pietarinen-Runtti, et al. (2000)
• Cellular and molecular mechanisms of asbestosis — B.T. Mossman, R. Gilbert, et al. (1986)
• Differential in vitro cellular response induced by exposure to synthetic vitreous fibers (SVFs) and asbestos crocidolite fibers — G. Cardinali, D. Kovacs, et al. (2006)

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