Observations on the carcinogenicity of asbestos fibers

Our plain-English summary of Observations on the carcinogenicity of asbestos fibers, by M.C. Jaurand (Annals of the New York Academy of Sciences, 1991).

The study

• Author: M.C. Jaurand
• Journal: Annals of the New York Academy of Sciences
• Published: 1991;643:258-70
• Type of article: Review
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This paper summarizes animal experiments and in vitro data carried out to study the oncogenic effects of asbestos fibers on mesothelial cells. An interpretation of the results is made in light of current statements on the carcinogenicity of asbestos fibers. Experimental results appear to show that the carcinogenicity of mineral fibers is a complex, multiparametric phenomenon. Chromosomal mutations and possibly oxygen derivatives are involved in the genesis of the fiber-induced neoplastic process and may be the result of the intrinsic fiber properties, size, and physicochemistry. The role of fiber solubility is discussed; it is suggested that additional experiments are necessary for a better understanding of the importance of solubility in the concept of biopersistence.

In plain English

In this review, the author summarized animal experiments and laboratory cell studies, largely from the author's laboratory, on the cancer-causing effects of asbestos fibers on mesothelial cells. Rats were given 20 mg of fiber by injection into the chest (pleural) cavity. For chrysotile samples, the percentage of rats developing mesothelioma rose with the number of long, thin fibers, meaning fibers at least 8 micrometers long and no more than 0.25 micrometers wide. When amosite, crocidolite and chrysotile were pooled, there was no correlation. Chrysotile from which magnesium had been leached with acid produced fewer mesotheliomas. In a short-term experiment, a chemically modified chrysotile, chrysophosphate, kept a stable magnesium-to-silicon ratio inside alveolar macrophages, while ordinary chrysotile was leached. Chrysophosphate caused tumors at the same order as ordinary chrysotile but was less toxic to cultured cells. In cultured rat pleural mesothelial cells, chrysotile caused abnormal chromosome numbers, and repeated treatment increased this. The author concluded that the carcinogenicity of mineral fibers appears to be a complex, multiparametric phenomenon. The author concluded that the chemical stability of fibers did not seem to directly affect the cancer process.

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: Review summarizing animal intrapleural-inoculation experiments and in vitro cell studies, mainly from the author's laboratory, interpreted alongside other published work
• Who was studied: Rats given intrapleural inoculations (groups of 30-40 animals per data point), and cultured rat pleural mesothelial cells; studies from the author's laboratory at INSERM U 139, Créteil, France
• Exposure: 20 mg intrapleural doses of chrysotile samples (Canadian, UICC A Rhodesian, superfine, short, milled, phosphated or 'chrysophosphate', and chrysotile leached with oxalic or hydrochloric acid), UICC amosite, UICC crocidolite, and leached amosite and crocidolite; in vitro, chrysotile given once at 5 µg/ml or in 11 further treatments at 2 µg/ml
• Main results:
  • For all chrysotile samples studied in rats, the percentage of mesotheliomas correlated with the logarithm of the number of fibers at least 8 µm long and no more than 0.25 µm in diameter (r = 0.661, p less than 0.01)
  • When data for amosite, crocidolite and chrysotile were pooled, there was no correlation between mesothelioma percentage and the number of such long, thin fibers (r = 0.159 for log number; r = 0.164 linear)
  • For unleached and acid-leached chrysotile, the percentage of mesotheliomas per long, thin fiber was inversely correlated with the percentage of magnesium leached (r = 0.857, p less than 0.05)
  • Mesothelioma percentage for phosphated and untreated Canadian chrysotile correlated with the number of fibers meeting Stanton's criteria (r = 0.812, p less than 0.05)
  • In cultured rat pleural mesothelial cells, both chrysotile and chrysophosphate induced a dose-dependent formation of aneuploid cells (cells with abnormal chromosome numbers)
  • Chrysophosphate was less toxic to cultured cells than unmodified chrysotile on a per-weight basis
  • After being taken up by alveolar macrophages, only about 30% of chrysotile fibers kept a magnesium-to-silicon ratio above 0.8, while the ratio for chrysophosphate remained stable for the duration of the experiment
  • The author described this stability as observed shortly after ingestion by the cells, in a short-term assay
  • After one chrysotile treatment, 38% of mesothelial cells were diploid (normal chromosome number) compared with 59% in untreated cultures
  • After 11 further chrysotile treatments, 48% of metaphases had 43 chromosomes and only 18% of cells were diploid
  • After about 40 passages, transformed cells were estimated at 5% in the repeatedly treated chrysotile cultures and 0% in the once-treated cultures; both series reached 100% after 30 additional passages
  • In untreated cultures, a 0.2% rate of transformed cells was detected after about 250 doublings
  • The author interpreted the experiments as indicating that fiber chemical stability did not directly affect the cancer process
• The authors' conclusion: The author concluded that the experimental results appear to show that the carcinogenicity of mineral fibers is a complex, multiparametric phenomenon
• Limitations the authors state:
  • The correlation between fiber size and mesothelioma was not absolute
  • The cell transformation study was incomplete: intermediate passages still needed testing
  • The chemical stability of chrysophosphate inside cells was shown only in a short-term assay
  • In vitro experiments and the inoculation method may show a fiber's intrinsic potency without taking the effect of time into account

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Mineral Fiber, biopersistence.

Related studies

• Interpretation of the carcinogenicity of amosite asbestos and ferroactinolite on the basis of retained fiber dose and characteristics in vivo — P.M. Cook, L.D. Palekar, et al. (1982)
• Carcinogenicity of fibers and films: a theory — V.E. Archer (1979)
• Perspectives on refractory ceramic fiber (RCF) carcinogenicity: comparisons with other fibers — H. Greim, M.J. Utell, et al. (2014)
• Variations in the carcinogenicity of tremolite dust samples of differing morphology — J.M. Davis, J. Addison, et al. (1991)
• Asbestos, asbestosis, and lung cancer: observations in Quebec chrysotile workers — B.W. Case, A. Dufresne (1997)
• Observations on environmental asbestos exposure in a high risk area — U. Sahin, O. Ozturk, et al. (2009)

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