Role of mutagenicity in asbestos fiber-induced carcinogenicity and other diseases

Our plain-English summary of Role of mutagenicity in asbestos fiber-induced carcinogenicity and other diseases, by S.X. Huang, M.C. Jaurand, D.W. Kamp, et al (Journal of Toxicology and Environmental Health. Part B, Critical Reviews, 2011).

The study

• Authors: S.X. Huang, M.C. Jaurand, D.W. Kamp, J. Whysner, T.K. Hei
• Journal: Journal of Toxicology and Environmental Health. Part B, Critical Reviews
• Published: 2011;14(1-4):179-245
• Type of article: Review
• Cited by: 113 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The cellular and molecular mechanisms of how asbestos fibers induce cancers and other diseases are not well understood. Both serpentine and amphibole asbestos fibers have been shown to induce oxidative stress, inflammatory responses, cellular toxicity and tissue injuries, genetic changes, and epigenetic alterations in target cells in vitro and tissues in vivo. Most of these mechanisms are believe to be shared by both fiber-induced cancers and noncancerous diseases. This article summarizes the findings from existing literature with a focus on genetic changes, specifically, mutagenicity of asbestos fibers. Thus far, experimental evidence suggesting the involvement of mutagenesis in asbestos carcinogenicity is more convincing than asbestos-induced fibrotic diseases. The potential contributions of mutagenicity to asbestos-induced diseases, with an emphasis on carcinogenicity, are reviewed from five aspects: (1) whether there is a mutagenic mode of action (MOA) in fiber-induced carcinogenesis; (2) mutagenicity/carcinogenicity at low dose; (3) biological activities that contribute to mutagenicity and impact of target tissue/cell type; (4) health endpoints with or without mutagenicity as a key event; and finally, (5) determinant factors of toxicity in mutagenicity. At the end of this review, a consensus statement of what is known, what is believed to be factual but requires confirmation, and existing data gaps, as well as future research needs and directions, is provided.

In plain English

This article was a review, not a new study. Writing as part of an NIEHS-funded workshop, the authors examined published laboratory, animal and human research on whether asbestos causes mutations (permanent, inheritable changes to genes or chromosomes) and how this relates to asbestos diseases. They included all six forms of asbestos: chrysotile and the amphiboles crocidolite, amosite, tremolite, anthophyllite and actinolite. Most of the evidence came from cells grown in the laboratory. The authors concluded that asbestos is clearly mutagenic in a variety of test systems and that asbestos-related cancer involves both mutation-causing and other pathways. Specific genetic changes occur in human mesothelioma tissue, but the authors said a direct causal link with asbestos-induced mutations had not been established. They judged that mutation plays no role in pleural plaques, that DNA damage but not mutation might contribute to asbestosis, and that there was some indication of a role in lung cancer. They wrote that the mutagenic effect of low doses was still unknown. They noted that many studies used doses higher than human exposure. They also noted that human data confirming the laboratory and animal findings on how asbestos causes mutations were inadequate.

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 in vitro, animal and human studies, ending in a consensus statement; part of an NIEHS-funded workshop
• Who was studied: Published studies in cultured cells, laboratory animals (mainly rats and mice) and humans (blood cells of exposed workers and tumor tissue), plus some studies of man-made fibers and erionite; most of the evidence on direct mutagenic effects came from cell studies
• Exposure: All six forms of asbestos: the amphiboles crocidolite, amosite, tremolite, anthophyllite and actinolite, and the serpentine fiber chrysotile
• Main results:
  • The authors judged asbestos to be clearly mutagenic across a variety of laboratory and animal test systems, inducing both gene and chromosomal mutations
  • Specific genetic changes are found in human mesothelioma, but the authors stated that a direct causal link between asbestos-induced mutations and mesothelioma has not been established in animals or humans
  • The authors stated that a direct link between asbestos-induced mutation and cancer is lacking
  • The authors concluded that mutation does not play a role in pleural plaques (or in diffuse pleural thickening)
  • For asbestosis, the authors suggested that DNA damage, but not mutation, might play a role
  • For lung cancer, the authors found some indication that mutation plays a role and said further study is necessary
  • According to the authors, the mutagenic effect of asbestos at low doses is unknown
  • The authors described whether there is a threshold dose for cancer as still controversial; they wrote that limited rodent inhalation evidence showed no threshold
• The authors' conclusion: The authors concluded that the existing literature indicates asbestos-induced cancer involves both mutagenic and nonmutagenic pathways
• Limitations the authors state:
  • In vivo evidence of mutation came from tumor tissue, which made it hard to establish that the mutations found caused the cancers
  • Many of the studies reviewed used concentrations higher than human occupational and environmental exposure
  • Few studies tested multiple doses, which limits any determination of a threshold
  • Many animal studies used injection into the abdomen or instillation into the windpipe, which is not the normal route of exposure
  • Human data are inadequate to validate the laboratory and animal findings on the mechanisms (oxidants, DNA damage, apoptosis, p53) by which asbestos causes mutations in lung target cells

Topics

Medical terms in this study, explained in our Lexicon: Serpentine Group, Amphibole Asbestos, Oxidative Stress, Carcinogenesis.

Related studies

• Perspectives on refractory ceramic fiber (RCF) carcinogenicity: comparisons with other fibers — H. Greim, M.J. Utell, et al. (2014)
• Determination of carcinogenic potential of mineral fibers by 8-hydroxydeoxyguanosine as a marker of oxidative DNA damage in mammalian cells — N. Murata-Kamiya, T. Tsutsui, et al. (1997)
• The carcinogenicity of WHO fibers of silicon carbide: SiC whiskers compared to cleavage fragments of granular SiC — K. Rödelsperger, B. Brückel (2006)
• A review of carcinogenicity studies of asbestos and non-asbestos tremolite and other amphiboles — J. Addison, E.E. McConnell (2008)
• Glutathione modulates the formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA100 induced by mineral fibres — P.J. Howden, S.P. Faux (1996)
• Health effects of asbestos and nonasbestos fibers — O.Y. Osinubi, M. Gochfeld, et al. (2000)

Browse more research in Journal of Toxicology and Environmental Health. Part B, Critical Reviews, or return to medical research.