Role of fibre characteristics on cytotoxicity and induction of anaphase/telophase aberrations in rat pleural mesothelial cells in vitro: correlations with in vivo animal findings

Our plain-English summary of Role of fibre characteristics on cytotoxicity and induction of anaphase/telophase aberrations in rat pleural mesothelial cells in vitro: correlations with in vivo animal findings, by M. Yegles, X. Janson, H.Y. Dong, et al (Carcinogenesis, 1995).

The study

• Authors: M. Yegles, X. Janson, H.Y. Dong, A. Renier, M.C. Jaurand
• Journal: Carcinogenesis
• Published: 1995;16(11):2751-8
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Thirteen samples of natural fibres and five samples of man-made fibres (MMF) were tested to determine their cytotoxicity and ability to produce chromosome missegregation in cultures in rat pleural mesothelial cells (RPMC). The natural samples included attapulgite, two amphiboles (amosite and crocidolite); seven consisted of chrysotile from various origins and three were obtained after chemical treatment of chrysotile. MMF included three refractory ceramic fibres (RCF) and two vitreous fibres (MMVF). All fibre samples were characterized by electron microscopic measurement of the fibre dimensions. Cytotoxicity was assayed on the basis of determination of mitochondrial integrity and chromosome missegregation by light microscopy examination of anaphases/telophases. The carcinogenic potency of 10 natural samples has been previously investigated using intrapleural inoculation in rats. It was therefore possible to establish correlations between in vitro and in vivo data obtained with the same set of samples. The various samples of chrysotile produced different in vitro effects, in agreement with the dispersion of response also observed in vivo. Cytotoxicity appears to be dependent on both fibre length and fibre diameter, as the longest or thickest fibres were the most toxic. The production of abnormal anaphases/telophases appears to depend on the presence of fibres of selected size, such as those previously defined by Stanton et al. (L > 8 micrograms; D < or = 0.25 microns); a threshold values was determined below which no abnormal anaphases/telophases were detected. This non-observable effect level was estimated to be 2.5 x 10(5) 'Stanton' fibres per cm2. There was no correlation between cytotoxicity and mesothelioma induction; in contrast, a correlation was found between the ability of a sample to produce chromosome missegregation in vitro and mesothelioma in vivo.

In plain English

This laboratory study exposed cultured rat pleural mesothelial cells to 18 fibre samples: attapulgite, amosite, crocidolite, ten chrysotile samples (three chemically treated), three refractory ceramic fibres and two man-made vitreous fibres. The authors measured cell killing and abnormal cell division (anaphase/telophase aberrations). The longest and thickest fibres killed the most cells. Amosite, oxalic-acid-leached chrysotile, a short Canadian chrysotile, and the ceramic and glass fibres caused no significant aberrations. UICC chrysotile induced more aberrations than crocidolite or amosite. Above about 2.5 x 10^5 'Stanton' fibres (longer than 8 micrometres and 0.25 micrometres or thinner) per square centimetre, all samples significantly increased aberrations; below that level, none did. The authors compared these results with earlier rat studies by their group in which 10 natural samples were injected into the pleural cavity. Cell killing did not correlate significantly with mesothelioma; aberrations per Stanton fibre did. The authors concluded that this cell test, combined with the aneuploidy test, might be a useful indicator of fibre genotoxicity and carcinogenicity. They noted the animal studies used a single high dose, the cell tests lower doses.

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 rat cells, with results compared to the same group's earlier animal (intrapleural injection) studies of 10 of the natural fibre samples
• Who was studied: Rat pleural mesothelial cells (RPMC) grown in culture, established in the authors' laboratory (INSERM, Créteil, France), tested with 13 natural and 5 man-made fibre samples
• Exposure: Natural fibres: attapulgite, amosite, crocidolite, seven chrysotile samples of various origins, and three chemically treated chrysotile samples (oxalic-acid-leached or phosphorylated). Man-made fibres: three refractory ceramic fibres and two vitreous fibres. Cells were exposed to a range of concentrations: 24 hours for the cell-viability (MTT) test and 48 hours for the anaphase/telophase test.
• Main results:
  • Among the mineral fibre samples, NIEHS chrysotile was the most toxic to cells.
  • The concentration leaving 75% of cells viable (IC75) was 37.1 micrograms per square centimetre for amosite and more than 100 micrograms per square centimetre for crocidolite.
  • The man-made fibre samples were more toxic to cells than the mineral fibres on a per-fibre basis.
  • Cell toxicity correlated with fibre length and also with fibre diameter (r = 0.89; P less than 0.01, Spearman's rank test).
  • Untreated control cultures showed an average of 3.4% (plus or minus 2.7%) abnormal anaphases, across 34 experiments.
  • UICC chrysotile was a stronger inducer of anaphase/telophase aberrations than crocidolite and amosite, both by weight and by total fibre number.
  • Amosite caused no significant anaphase aberrations.
  • Oxalic-acid-treated UICC chrysotile caused no abnormalities.
  • Short Canadian chrysotile fibres (SCF) caused no anaphase aberrations.
  • The ceramic and glass fibres, which were long and thick, did not produce anaphase aberrations.
  • Only chrysotile samples caused a significant increase in chromosome bridges, ranging from 4% to 7.7% compared to untreated controls.
  • Above about 2.5 x 10^5 Stanton fibres per square centimetre, all samples produced a significant increase in anaphase abnormalities; below that level, none did.
  • The comparison with animal data used the group's earlier rat intrapleural injection studies, which covered 10 of the natural samples.
  • When compared with mesothelioma rates from those rat studies, cell toxicity showed no significant correlation. The rate of anaphase aberrations per Stanton fibre was significantly correlated (probability 0.0075, Spearman's rank test). No other way of expressing the dose gave a significant correlation.
  • Both active and heat-inactivated catalase (an antioxidant enzyme) reduced anaphase abnormalities, so the test did not show a role for oxygen derivatives.
• The authors' conclusion: The authors concluded that, because the anaphase/telophase test correlated well with the animal data when expressed per Stanton fibre, this test combined with the aneuploidy test might be a useful indicator of fibre genotoxicity and carcinogenicity.
• Limitations the authors state:
  • All thin and small samples were mineral fibres, while most thick and all large samples were man-made fibres; the authors said this may bias the size–toxicity correlation.
  • The animal studies generally tested a single high dose, while the cell experiments used a range of relatively low doses.
  • Chemical treatment also changed fibre size, which may account for the differences seen with treated fibres.
  • The correlations might differ for inhalation exposure, which the authors could not assess from the published literature.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Santa Rita mine, Joaquin Ridge near Coalinga, California

All asbestos mines

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite, Crocidolite.

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Palygorskite (Attapulgite), Amphibole Group, Amosite, Crocidolite, Chrysotile, Vitreous, Carcinogenic.

Related studies

• Induction of metaphase and anaphase/telophase abnormalities by asbestos fibers in rat pleural mesothelial cells in vitro — M. Yegles, L. Saint-Etienne, et al. (1993)
• Induction by asbestos fibers of anaphase abnormalities: mechanism for aneuploidy induction and possibly carcinogenesis — T.W. Hesterberg, J.C. Barrett (1985)
• Cytotoxicity and anaphase aberrations induced by mineral fibres in cultured human mesothelial cells — K. Pelin, K. Husgafvel-Pursiainen, et al. (1992)
• Role of oxygen derivatives in the cytotoxicity and DNA damage produced by asbestos on rat pleural mesothelial cells in vitro — H. Dong, A. Buard, et al. (1994)
• Metsovo-tremolite asbestos fibres: in vitro effects on mutation, chromosome aberration, cell transformation and intercellular communication — K. Athanasiou, S.H. Constantopoulos, 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)

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