Asbestos-associated chromosomal changes in human mesothelial cells

Our plain-English summary of Asbestos-associated chromosomal changes in human mesothelial cells, by J.F. Lechner, T. Tokiwa, M. LaVeck, et al (Proceedings of the National Academy of Sciences of the United States of America, 1985).

The study

• Authors: J.F. Lechner, T. Tokiwa, M. LaVeck, W.F. Benedict, S. Banks-Schlegel, H. Yeager, A. Banerjee, C.C. Harris
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Published: 1985;82(11):3884-8
• Cited by: 179 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Replicative cultures of human pleural mesothelial cells were established from noncancerous adult donors. The cells exhibited normal mesothelial cell characteristics including keratin, hyaluronic acid mucin, and long branched microvilli, and they retained the normal human karyotype until senescence. The mesothelial cells were 10 and 100 times more sensitive to the cytotoxic effects of asbestos fibers than normal human bronchial epithelial or fibroblastic cells, respectively. In addition, cultures of mesothelial cells that survived two cytotoxic exposures of amosite fibers were aneuploid with consistent specific chromosomal losses indicative of clonal origin. These aneuploid cells exhibit both altered growth control properties and a population doubling potential of greater than 50 divisions beyond the culture life span (30 doublings) of the control cells.

In plain English

This was a laboratory study of human cells, not of people. The authors grew pleural mesothelial cells from fluid drained from the chests of adults without cancer, for example people with congestive heart failure. They measured the fiber dose that cut the cells' ability to form colonies by half: chrysotile 0.06, amosite 0.10, crocidolite 0.40 and glass fibers 1.02 micrograms per square centimeter of dish. For amosite, the authors compared this with earlier figures of 1.02 for bronchial epithelial cells and 10.40 for bronchial fibroblastic cells. Cultures exposed twice to amosite developed abnormal-looking cells. By the fifth passage, all exposed cells had abnormal chromosome sets. All 18 hypodiploid metaphases karyotyped were missing chromosome 11 or 21, which the authors said strongly suggests a clonal origin. Unexposed cultures kept normal chromosomes and stopped growing during the fourth subculture. Exposed cultures kept multiplying for more than 50 further population doublings. Cells from four other donors behaved similarly. Injected into nude mice, the altered cells produced no tumors within 18 months. The authors concluded that these changes were insufficient to make the cells tumorigenic.

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 cultured human cells, with a tumor test of the altered cells in athymic nude mice
• Who was studied: Human pleural mesothelial cells grown from pleural effusions of noncancerous adult donors who needed thoracentesis (e.g., congestive heart failure). Repeat experiments used cultures from four other noncancerous donors.
• Exposure: UICC standard reference chrysotile, amosite and crocidolite asbestos, plus glass fibers, at increasing doses for cytotoxicity tests. For the long-term studies, two exposures to amosite at 0.30 micrograms per square centimeter of dish surface.
• Main results:
  • In mesothelial cells, the dose (micrograms of fiber per square centimeter of dish) that reduced colony-forming efficiency by 50% was: chrysotile 0.06, amosite 0.10, crocidolite 0.40, glass fibers 1.02.
  • For comparison, the authors cited an earlier study (their reference 18) giving amosite 50% cytotoxic doses of 1.02 for bronchial epithelial cells and 10.40 for bronchial fibroblastic cells.
  • Unexposed control cultures reached senescence during the fourth subculture. Amosite-exposed cultures kept multiplying for more than 19 further subculturings (more than 50 population doublings).
  • Unexposed cultures kept a normal diploid karyotype until senescence. By the fifth passage, all amosite-exposed cells were pseudodiploid or aneuploid.
  • Of 45 metaphases analyzed at passage 5 in exposed cells, the majority were hypodiploid with a mode of 42 chromosomes.
  • All 18 hypodiploid metaphases that were karyotyped were missing chromosome 11 or chromosome 21. The authors said this strongly suggests a clonal origin.
  • Dicentric chromosomes were found in 100% of the hyperdiploid cells and in a printed '-50%' of the hypodiploid cells (probably about 50%).
  • The chromosomally abnormal cells had a generation time of 50 hr, which the authors reported as significantly greater than the 28 hr of early-passage normal mesothelial cells.
  • Cultures from four other noncancerous donors behaved similarly: they became morphologically transformed and showed chromosomal rearrangements, including dicentrics.
  • Altered cells from the 11th passage after the second amosite exposure were injected under the skin of adult athymic nude mice (5 x 10^6 cells per mouse; 9-20 mice per experiment). No tumors arose within 18 months.
• The authors' conclusion: The authors concluded that asbestos induced clonally derived aneuploid cells with abnormal growth control, including slower multiplication and a greatly extended doubling potential. They concluded that these alterations were insufficient to make the cells tumorigenic.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile, Lung cancer, Mesothelioma, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Hyaluronic Acid, Amosite.

Related studies

• Specificity of asbestos-induced chromosomal aberrations in short-term cultured human mesothelial cells — K. Olofsson, J. Mark (1989)
• Chromosomal changes induced by chrysotile fibres or benzo-3,4-pyrene in rat pleural mesothelial cells — M.C. Jaurand, L. Kheuang, et al. (1986)
• Gene expression profiling and gene copy-number changes in malignant mesothelioma cell lines — C. Zanazzi, R. Hersmus, et al. (2007)
• Oxidant stress responses in human pleural mesothelial cells exposed to asbestos — Y.M. Janssen, J.P. Marsh, et al. (1994)
• Dielectric changes in membrane properties and cell interiors of human mesothelial cells in vitro after crocidolite asbestos exposure — E. Dopp, L. Jonas, et al. (2000)
• 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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