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

Our plain-English summary of 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, by E. Dopp, M. Schuler, D. Schiffmann, et al (Mutation Research, 1997).

The study

• Authors: E. Dopp, M. Schuler, D. Schiffmann, D.A. Eastmond
• Journal: Mutation Research
• Published: 1997;377(1):77-87
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This article describes the induction of micronuclei, hyperdiploidy and chromosome breakage in human amniotic cells in vitro by amosite, chrysotile and crocidolite asbestos, and ceramic fibers. The response of human (amniotic fluid cells) and rodent (Syrian hamster embryo fibroblasts, SHE) cells to fiber treatment was compared using the micronucleus assay. The data of the rodent studies were taken from a previous investigation (Dopp, E. et al. (1995) Environ. Health Perspect., 103, 268-271). All types of mineral fibers caused a significant increase of micronucleated cells. The kinetochore analysis revealed that all three types of asbestos and ceramic fibers yielded similar effects. Approximately 50% of the induced micronuclei were kinetochore-negative indicating formation through clastogenic events. Human amniotic cells were much less susceptible than SHE cells to the induction of micronuclei by mineral fibers. This again demonstrates that SHE cells are more susceptible to chromosomal changes than human amniotic fluid cells. The application of fluorescence in situ hybridization (FISH) with tandem DNA probes yielded more detailed information about specific structural chromosome aberrations in the 1 (cen-q12) and 9 (cen-q12) regions and about abnormal numbers of chromosomes in interphase human amniotic fluid cells. Using this FISH approach we found a statistically significant increase of chromosomal breakage in the pericentric heterochromatin regions of chromosomes 1 and 9 in interphase human amniotic cells after exposure to asbestos and ceramic fibers compared to control cells. The number of hyperdiploid cells was also significantly increased. Our results show that asbestos fibers as well as ceramic fibers are inducers of structural and numerical chromosomal aberrations in human amniotic fluid cells.

In plain English

This was a laboratory study on cultured human amniotic fluid cells, not on people. The authors treated the cells for 48 hours with amosite, chrysotile or crocidolite asbestos, with ceramic fibers, or with gypsum as a negative control, then looked for genetic damage. All fiber types increased micronuclei, which are small bits of genetic material outside the cell nucleus. Chrysotile produced up to 70 per 2000 cells and amosite up to 58, against 25 in controls. About half of the induced micronuclei pointed to chromosome breakage. Using fluorescent DNA labels, the authors found significantly more breaks near the centre of chromosome 1 in every fiber-treated culture, for example 24.0 per 1000 cells with crocidolite against 7.7 in untreated cells. On chromosome 9, breaks were significantly increased for all fibers except amosite. Cells with extra chromosome copies were also significantly more common. Compared with earlier hamster-cell data, the human cells formed 2 to 3 times fewer micronuclei after asbestos; with ceramic fibers they also formed fewer, but the gap was smaller. The authors concluded that asbestos and ceramic fibers are relatively weak but effective inducers of these changes in these cells.

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: In vitro laboratory experiment on cultured human cells. Micronucleus results were compared with hamster-cell (SHE) data from the authors' earlier study.
• Who was studied: Human amniotic fluid cells bought from Coriell Cell Repositories (USA). Micronucleus data points were the mean of 3 cultures with 2000 nuclei each. FISH scoring used 1000 nuclei per case.
• Exposure: Amosite, crocidolite and Rhodesian chrysotile (UICC standard) asbestos, and ceramic fibers, for 48 hours. Gypsum was the negative control. For the FISH tests, asbestos was used at 1 and ceramic fibers at 5 (units printed as mg/cm2). About 5% of asbestos fibers were 5 or more in length. Ceramic fibers were longer and thicker than the asbestos fibers.
• Main results:
  • Micronuclei were significantly increased at concentrations 1.0 and 5.0 with amosite and chrysotile: chrysotile up to 70 and amosite up to 58 micronuclei per 2000 cells, versus 25 per 2000 in control. Crocidolite reached 59 per 2000 cells at 5.0, and ceramic fibers up to 60 per 2000 at 0.5. Untreated controls are also given as 30 to 32 per 2000.
  • Kinetochore staining gave similar results for all three asbestos types and ceramic fibers. Kinetochore-positive micronuclei rose more than 3-fold and kinetochore-negative ones about 2-fold. In fiber-treated cells, 46.0% to 48.3% of micronuclei were kinetochore-positive, versus 34.8% with gypsum and 33.5% in controls.
  • Chromosome 1 breakage was 7.7 to 8.5 per 1000 cells in untreated and gypsum-treated cultures. It was significantly higher in all fiber-treated cultures: crocidolite 24.0 (p less than or equal to 0.001), and ceramic 17.9, chrysotile 16.6 and amosite 16.0 per 1000 cells (p less than or equal to 0.01).
  • Hyperdiploid cells (mainly tetrasomic for chromosome 1) were significantly increased with all fibers: ceramic p less than or equal to 0.001, chrysotile p less than or equal to 0.01, crocidolite and amosite p less than or equal to 0.05.
  • Chromosome 9 breakage was highest with crocidolite (22.0 per 1000 cells, p less than or equal to 0.01). Ceramic fibers (21.0) and chrysotile (18.2) followed, with p less than or equal to 0.05. Amosite (18.0) was not significant. Controls were 11.0 and gypsum 10.0 per 1000 cells. Hyperdiploidy for chromosome 9 was significantly increased for all fibers.
  • For asbestos, micronuclei induced in SHE (hamster) cells in the earlier study were 2- to 3-fold higher than in the human amniotic cells.
  • For ceramic fibers, micronuclei in the human cells were also fewer than in SHE cells, but the difference was not as large as for asbestos.
• The authors' conclusion: The authors concluded that asbestos and ceramic fibers are relatively weak, but effective, inducers of hyperdiploidy and of chromosome breakage near the centres of chromosomes 1 and 9 in cultured human amniotic fluid cells.
• Limitations the authors state:
  • The authors note that the background rate of hyperdiploid cells in their control cultures (2.0 to 2.5%) was higher than in some other cell types.
  • The authors note that micronucleus formation by ceramic fibers did not seem strictly connected to fiber concentration.

Topics

Medical terms in this study, explained in our Lexicon: Micronuclei, Amosite, Chrysotile, Crocidolite, Fibroblast, Mineral Fiber, Fluorescence In Situ Hybridization (FISH).

Related studies

• Analysis of chromosomal alterations induced by asbestos and ceramic fibers — E. Dopp, D. Schiffmann (1998)
• Aberrations of chromosome 19 in asbestos-associated lung cancer and in asbestos-induced micronuclei of bronchial epithelial cells in vitro — S.T. Ruosaari, P.E. Nymark, et al. (2008)
• Smoking enhances asbestos-induced genotoxicity, relative involvement of chromosome 1: a study using multicolor FISH with tandem labeling — M. Lohani, E. Dopp, et al. (2002)
• Chromosome nondisjunction during bipolar mitoses of binucleated intermediates promote aneuploidy formation along with multipolar mitoses rather than chromosome loss in micronuclei induced by asbestos — T. Zhang, L. Lv, et al. (2017)
• Genomic changes of chromosomes 8p23.1 and 1q21: Novel mutations in malignant mesothelioma — G. Serio, L. Vimercati, et al. (2018)
• Mitotic disturbances and micronucleus induction in Syrian hamster embryo fibroblast cells caused by asbestos fibers — E. Dopp, J. Saedler, et al. (1995)

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