Specificity of asbestos-induced chromosomal aberrations in short-term cultured human mesothelial cells

Our plain-English summary of Specificity of asbestos-induced chromosomal aberrations in short-term cultured human mesothelial cells, by K. Olofsson, J. Mark (Cancer Genetics and Cytogenetics, 1989).

The study

• Authors: K. Olofsson, J. Mark
• Journal: Cancer Genetics and Cytogenetics
• Published: 1989;41(1):33-9
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Short-term cultured normal human mesothelial cells were exposed for 48 hours to three different asbestos compounds, crocidiolite, chrysotile, and amosite. In the concentration used (0.01 mg/ml) all three asbestiform minerals caused, within a few days, a significant increase of cells showing numerical and/or structural abnormalities. The abnormalities were analyzed in detail using banding techniques. The results were compared with the cytogenetic observations in 52 published cases of mesotheliomas. This comparison revealed only a few similarities as regards numerical deviations. The structural rearrangements in asbestos-exposed cultures, however, in many instances involved chromosome types and chromosome regions preferentially affected in mesotheliomas.

In plain English

This laboratory study examined chromosomes in normal mesothelial cells cultured from the chest fluid of four women, aged 52 to 86, not suspected of having cancer. Cultures were exposed for 48 hours to UICC crocidiolite (as the article spells crocidolite), chrysotile or amosite at 0.01 mg/ml. A tenfold higher dose of crocidiolite or chrysotile had killed almost all cells. The authors reported that all three minerals caused, within days, a significant increase in cells with abnormal chromosomes, though the article shows no statistical test. Changes in chromosome number were mostly losses. Structural changes, mainly deletions and translocations, were each unique. Only one crocidiolite culture showed a clear group of identical cells, with an extra chromosome 7. The amosite preparation had few normal cells. Two of four unexposed control cultures showed one abnormal cell each. Compared with 52 published mesotheliomas, number changes showed only a few similarities. However, many structural changes involved chromosomes and regions often affected in mesotheliomas. The authors concluded that further changes must be added before a tumor develops. Cultures stopped growing after about ten days, so long-term cultures could not be studied.

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) experiment on human cells in short-term culture, with unexposed control cultures and a comparison against 52 published mesothelioma cases
• Who was studied: Normal mesothelial cells cultured from pleural effusions of four female patients (P1-P4) aged 86, 81, 52 and 81. The patients had their chest fluid drained for reasons other than suspected malignancy, mostly congestive heart failure. The work was done at the Department of Pathology and Cytogenetics, Central Hospital, Skövde, Sweden.
• Exposure: UICC crocidiolite (blue asbestos), UICC chrysotile (white asbestos) and UICC amosite (brown asbestos). Crocidiolite and chrysotile were first tested at 0.1 mg/ml for 48 hours, which caused almost total cell death within a few days. The experiments therefore used 0.01 mg/ml for 48 hours for all three minerals.
• Main results:
  • The authors stated that the asbestos compounds easily and rapidly caused a significant increase of both numerical and structural aberrations. No statistical test is reported in the article.
  • Apart from a single cell with a doubled normal karyotype, all exposed cultures showed variation in chromosome number in the near-diploid range.
  • In most cultures the numerical variation was mainly hypodiploid and consisted mostly of chromosome losses. All chromosome types except #11 were affected.
  • In one crocidiolite-exposed preparation (preparation 3), the 47-chromosome cells all had an extra chromosome 7. This was the only clear clonal proliferation in the experiments.
  • Structural rearrangements were mostly deletions and, often, reciprocal translocations. No dicentrics were seen, and only one cell had a ring chromosome.
  • All structural rearrangements were unique, with a tendency for chromosome 1 to be involved more often.
  • Crocidiolite- and chrysotile-exposed cultures showed roughly equal numerical and structural variation.
  • In the amosite-exposed culture, cells with a normal karyotype were rare, and structural rearrangements outnumbered numerical deviations.
  • Unexposed control cultures from each patient were checked: 20 cells counted and 10 karyotyped per patient. P1 and P3 showed only normal karyotypes. P2 and P4 each had one abnormal cell, which the authors thought might relate to repeated previous lung x-ray examinations.
  • The pattern of numerical deviations differed from that in published mesotheliomas. The authors suggested this might merely reflect decade-long selection processes.
  • Many breakpoints of asbestos-induced marker chromosomes fell on chromosome types preferentially involved in the 52 published mesotheliomas, for instance chromosomes 1, 4, 6, 9, 13 and 17.
  • For these chromosomes and for chromosomes 2, 3, 5, 8, 12, 14, 18 and 19, one or several regions preferentially involved in mesotheliomas were also affected in asbestos-induced marker chromosomes.
  • The short arm of chromosome 3 was the region most often affected in mesotheliomas but was rarely rearranged in the exposed cells. The authors suggested 3p changes might be secondary changes occurring late in tumor progression.
• The authors' conclusion: The authors concluded that asbestos-exposed mesothelial cells rapidly develop many numerical and structural aberrations, and that some of these fit recurrent abnormalities recorded for mesotheliomas. Given the long latency of mesothelioma, they concluded that further gross chromosomal or submicroscopic changes must be superimposed to result in a malignant tumor.
• Limitations the authors state:
  • All exposed cultures stopped growing after the tenth day, so no long-term cultures could be analyzed.
  • Only one informative preparation was obtained for amosite, 9 days after exposure.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Chrysotile, Amosite, Asbestiform, Mesothelioma.

Related studies

• Attenuation of oxidative stress and chromosomal aberrations in cultured macrophages and pulmonary cells following self-sustained high temperature synthesis of asbestos — S. La Maestra, R.T. Micale, et al. (2020)
• Chromosomal aberrations induced by chrysotile and crocidolite in human lymphocytes in vitro — F. Valerio, M. de Ferrari, et al. (1983)
• Chromosomes and chromosomal evolution in human mesotheliomas as reflected in sequential analyses of two cases — G. Stenman, K. Olofsson, et al. (1986)
• Cytotoxicity and anaphase aberrations induced by mineral fibres in cultured human mesothelial cells — K. Pelin, K. Husgafvel-Pursiainen, et al. (1992)
• Chromosomal changes induced by chrysotile fibres or benzo-3,4-pyrene in rat pleural mesothelial cells — M.C. Jaurand, L. Kheuang, et al. (1986)
• Cytogenetic response to asbestos fibers in cultured human primary mesothelial cells from 10 different donors — K. Pelin, A. Hirvonen, et al. (1995)

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