Mechanisms of fiber-induced genotoxicity

Our plain-English summary of Mechanisms of fiber-induced genotoxicity, by M.C. Jaurand (Environmental Health Perspectives, 1997).

The study

• Author: M.C. Jaurand
• Journal: Environmental Health Perspectives
• Published: 1997;105 Suppl 5(Suppl 5):1073-84
• Type of article: Review
• Cited by: 106 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The mechanisms of particle-induced genotoxicity have been investigated mainly with asbestos fibers. The results are summarized and discussed in this paper. DNA damage can be produced by oxidoreduction processes generated by fibers. The extent of damage yield depends on experimental conditions: if iron is present, either on fibers or in the medium, damage is increased. However, iron reactivity does not explain all the results obtained in cell-free systems, as breakage of plasmid DNA was not directly associated with the amount of iron released by the fibers. The proximity of DNA to the site of generation of reactive oxygen species (ROS) is important because these species have an extremely short half-life. Damage to cellular DNA can be produced by oxidoreduction processes that originate from cells during phagocytosis. Secondary molecules that are more stable than ROS are probably involved in DNA damage. Oxidoreduction reactions originating from cells can induce mutations. Genotoxicity is also demonstrated by chromosomal damage associated with impaired mitosis, as evidenced by chromosome missegregation, spindle changes, alteration of cell cycle progression, formation of aneuploid and polyploid cells, and nuclear disruption. In some of these processes, the particle state and fiber dimensions are considered important parameters in the generation of genotoxic effects.

In plain English

This article was a review of laboratory research on how fibers, mainly asbestos, may damage genetic material. It covered studies of DNA in test tubes, bacteria, rodent and human cells, and a few animal studies. It did not study people. The author reported that most standard gene mutation tests had found fibers not directly mutagenic. Newer tests found that asbestos could produce DNA damage through reactive oxygen species, with iron playing a part, although iron-free fibers such as RCF1 could also damage DNA. Chromosome damage was found more often in rodent cells than in human cells. For example, 10 of 10 rodent-cell studies with chrysotile showed structural chromosome damage, compared with 2 of 6 human-cell studies. Samples rich in long, thin fibers tended to disrupt cell division, while short fibers that followed cell movements did not impair chromosome movement. The author noted that studies of DNA breakage in cells gave inconsistent results, possibly because of different cell types and methods. The author concluded that evidence had accumulated that fibers are genotoxic agents.

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 of published laboratory (mainly in vitro) studies on the genotoxicity of fibers and its mechanisms
• Who was studied: Published experiments using cell-free DNA, bacteria, and rodent and human cell cultures (for example Chinese hamster ovary cells, embryo fibroblasts, lung fibroblasts, epithelial cells and pleural mesothelial cells), plus a few in vivo studies in mice and Drosophila; no human subjects
• Exposure: Mainly asbestos fibers (crocidolite, chrysotile, amosite, anthophyllite, tremolite), with fewer data on man-made fibers such as glass fibers, refractory ceramic fibers (RCF) and man-made vitreous fibers (MMVF), and on erionite
• Main results:
  • In most of the gene mutation studies reviewed, fibers were not directly mutagenic
  • In cell-free systems, blocking iron with the chelator desferrioxamine protected against DNA damage by asbestos, but iron-free fibers such as RCF1 could still produce DNA damage
  • Studies showing structural chromosome damage, counted as studies with positive findings out of studies done: rodent cells 7/8 for crocidolite and 10/10 for chrysotile; human cells 1/5 for crocidolite and 2/6 for chrysotile. Studies showing numerical chromosome changes and polyploidy: rodent cells 12/12 for crocidolite and 8/8 for chrysotile; human cells 2/6 for crocidolite and 4/7 for chrysotile
  • Fiber samples enriched with long, thin fibers tended to produce abnormal anaphases (disturbed cell division)
  • In the observations of cell division described, short fibers that followed cell movements did not impair chromosome migration
  • In vivo, feeding mice asbestos did not produce chromosome abnormalities in germ cells, while in Drosophila fed fibers, asbestos and RCFs produced chromosomal changes
• The authors' conclusion: The author concluded that evidence has accumulated that fibers are genotoxic agents, based on their ability to produce DNA and chromosome damage
• Limitations the authors state:
  • Studies of DNA breakage in cells gave inconsistent results, possibly because of differing cell types and methods of analysis
  • Experimental conditions for synthetic fibers were not uniform enough between studies to allow comparisons between fiber types
  • Several human-cell studies used lymphocytes, which cannot take up fibers by phagocytosis
  • Few in vivo studies had been conducted

Topics

Medical terms in this study, explained in our Lexicon: Genotoxicity, Reactive Oxygen Species (ROS), Phagocytosis, Fiber Dimensions.

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