Analysis of chromosomal alterations induced by asbestos and ceramic fibers

Our plain-English summary of Analysis of chromosomal alterations induced by asbestos and ceramic fibers, by E. Dopp, D. Schiffmann (Toxicology Letters, 1998).

The study

• Authors: E. Dopp, D. Schiffmann
• Journal: Toxicology Letters
• Published: 1998;96-97:155-62
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos and other mineral fibers have long been known as carcinogenic agents. However, the primary mechanisms of fiber-induced carcinogenesis still remain unclear. We have investigated mitotic disturbances caused by amosite, crocidolite, and chrysotile in Syrian hamster embryo (SHE) fibroblasts. We also analyzed micronucleus formation as a result of mitotic disturbances, and carried out a characterization of the induced micronucleus population by kinetochore staining. In addition, the spindle fiber morphology was examined. Supravital UV-microscopy was used to analyze changes in chromatin structure, impaired chromatid separation and blocked cytokinesis. All three fiber types induced micronuclei in SHE cells with a high frequency (up to 200 MN/2000 cells; dose range: 0.1-5.0 microg/cm2) in a dose-dependent manner with a maximum between 48 and 66 h. Kinetochore staining revealed that 48% of fiber-induced micronuclei reacted positively. Furthermore, spindle deformation was observed in cells with disturbed meta- and anaphases while the spindle fiber morphology appeared unchanged. Our results show that asbestos fibers may cause both loss as well as breakage of chromosomes in the absence of direct interaction with spindle fibers. In addition, we analyzed the induction of micronuclei, hyperdiploidy and chromosome breakage in human amniotic fluid cells (AFC) in vitro by amosite, chrysotile and crocidolite asbestos and ceramic fibers. The response of human (AFC) and rodent (SHE) cells to fiber treatment was compared using the micronucleus assay. AFC were much less susceptible than SHE cells to the induction of micronuclei by mineral fibers. The application of fluorescence in situ hybridization (FISH) with tandem DNA probes yielded more detailed informations about specific structural chromosome aberrations in the 1(cen-q12) and 9(cen-q12) regions and about abnormal numbers of chromosomes in interphase AFC. Using this FISH approach we found a statistically significant increase of chromosomal breakage in the pericentric heterochromatin regions of chromosomes 1 and 9 in AFC after exposure to asbestos and ceramic fibers. The number of hyperdiploid cells was also significantly increased. These results show that asbestos as well as ceramic fibers are inducers of structural and numerical chromosomal alterations.

In plain English

In this study of cultured cells, not people, the authors exposed Syrian hamster embryo cells and human amniotic fluid cells to amosite, crocidolite and chrysotile asbestos and ceramic fibers. They counted micronuclei (small extra nuclei signalling chromosome damage), chromosome breaks and extra chromosome copies. All three asbestos types produced micronuclei in hamster cells, up to 200 per 2000 cells, rising with dose and peaking between 48 and 66 hours. Amosite gave the highest micronucleus frequency at the lowest concentration. In these asbestos-treated hamster cells, 48% of micronuclei stained positive for kinetochores (chromosome attachment points). With ceramic fibers, hamster cell micronuclei came mainly from chromosome breakage, a pattern the authors did not see in human cells. Hamster cells formed about three times more micronuclei than human cells. In human cells, asbestos and ceramic fibers significantly increased breakage in the examined regions near the centres of chromosomes 1 and 9, compared with untreated or gypsum-treated cells. Cells with extra copies, mainly four copies of chromosome 1, also rose significantly. The authors concluded that asbestos and ceramic fibers induce structural and numerical chromosomal alterations.

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: Laboratory (in vitro) cell culture experiment
• Who was studied: Cultured cells, not people: Syrian hamster embryo (SHE) fibroblasts from 13-day-old embryos, and human amniotic fluid cells (AFC) bought from Coriell Cell Repositories (USA)
• Exposure: Amosite, crocidolite and Rhodesian chrysotile asbestos (UICC standard samples) and ceramic fibers, added to the cell cultures. Gypsum was used as a negative control in the chromosome breakage tests.
• Main results:
  • In hamster (SHE) cells, all three asbestos types induced micronuclei at up to 200 per 2000 cells. The effect rose with dose and peaked between 48 and 66 hours.
  • In SHE cells, amosite was the most potent fiber, giving the highest micronucleus frequency at the lowest concentration, compared with crocidolite and chrysotile.
  • In the asbestos experiments in hamster (SHE) cells, the authors reported that 48% of fiber-induced micronuclei reacted positively in kinetochore staining.
  • In SHE cells treated with ceramic fibers, micronuclei arose primarily from chromosome breakage (clastogenic events). The authors did not see this pattern of micronucleus formation in human amniotic fluid cells. Chromosome breakage in the human cells after ceramic fibers was still increased, as shown by the FISH results.
  • In SHE cells, spindle deformation was seen in cells with disturbed cell division, but spindle fiber morphology appeared unchanged.
  • In SHE cells treated with ceramic fibers, micronucleus frequency peaked first at 18 to 24 hours and again at 72 hours.
  • Hamster (SHE) cells formed about three times more micronuclei than human amniotic fluid cells.
  • Ceramic fibers also induced micronuclei in human amniotic fluid cells.
  • In human amniotic fluid cells, breakage was significantly increased after asbestos and ceramic fibers in the pericentric heterochromatin regions of chromosomes 1 and 9, the regions examined by FISH (fluorescent DNA probes).
  • In human amniotic fluid cells, breakage in the labeled chromosome region was 7.7 to 8.5 per 1000 cells in untreated and gypsum-treated cultures. It was significantly higher after every fiber treatment.
  • In human amniotic fluid cells, the number of hyperdiploid cells (cells with extra chromosome copies, mainly four copies of chromosome 1) was significantly increased compared with untreated and gypsum-treated cultures.
• The authors' conclusion: The authors concluded that asbestos as well as ceramic fibers are inducers of structural and numerical chromosomal alterations. They also concluded that asbestos fibers may cause both loss and breakage of chromosomes without directly interacting with spindle fibers.

Topics

Medical terms in this study, explained in our Lexicon: Mineral Fiber, Carcinogenic, Carcinogenesis, Amosite, Crocidolite, Chrysotile, Fibroblast, Fiber Morphology.

Related studies

• Induction of micronuclei, hyperdiploidy and chromosomal breakage affecting the centric/pericentric regions of chromosomes 1 and 9 in human amniotic fluid cells after treatment with asbestos and ceramic fibers — E. Dopp, M. Schuler, et al. (1997)
• Asbestos, chromosomal deletions, and tumor suppressor gene alterations in human malignant mesothelioma — S.S. Murthy, J.R. Testa (1999)
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