Carcinogenesis and related cell and tissue responses to asbestos: a review

Our plain-English summary of Carcinogenesis and related cell and tissue responses to asbestos: a review, by B.T. Mossman (The Annals of Occupational Hygiene, 1994).

The study

• Author: B.T. Mossman
• Journal: The Annals of Occupational Hygiene
• Published: 1994;38(4):617-24, 423
• Type of article: Review
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A review of the literature reveals that chrysotile asbestos has a mulitiplicity of effects on cells and tissues which can provide a framework for assessment of its role(s) in initiation, promotion, or as a co-carcinogen which acts in concert with chemical carcinogens found in cigarette smoke in the development of lung cancer. Several caveats important in the interpretation of these data include the general lack of dose-response protocols both for in vivo and for in vitro studies as well as the absence, in many studies, of minerals which are appropriate positive or negative controls based on epidemiological data in man. Other factors which may account for disparities in results between studies include the use of different preparations of chrysotile fibres with distinct chemical and physical compositions and different cell types and species. Whether chrysotile is an initiator of lung cancer or mesothelioma in human cells is unclear, as evidence of chromosomal aberrations in human bronchial epithelial cells are for the most part negative (Kodoma et al., 1993; see Mossman, B., this Workshop): only one study employing pleural mesothelial cells from four individuals, two of whom exhibited chromosomal abnormalities before exposure to asbestos, has documented chromosomal changes with chrysotile, crocidolite and amosite asbestos, and this study did not use a non-pathogenic dust as a negative control. Studies using human lymphocytes show chromosomal changes after exposure to latex beads or chrysotile at equal weight concentrations (Korkina et al., 1992; see Mossman, B., this Workshop). Lastly, although both chrysotile and crocidolite asbestos demonstrated dose-dependent increase in aberrant anaphases in an SV40 T antigen-transformed human mesothelial cell line (Pelin et al., 1992, see Mossman, B., this Workshop), erionite, a potent mesotheliomagenic fibre in rodents and humans, caused no aberrations in this bioassay. Several studies have been performed to determine the interactions of chrysotile with rodent cells or isolated bacterial DNA. Results in a number of bioassays have been positive, but chrysotile is less potent on a fibre number comparative basis than crocidolite and no-observed-effect-levels (NOELs) have been observed in several systems. Cell proliferation by asbestos may be a more relevant phenomenon to tumour development and promotion, and the ability of chrysotile to stimulate cell proliferation, using a number of biomarkers, has been demonstrated both in vitro and after inhalation by rats.(ABSTRACT TRUNCATED AT 400 WORDS)

In plain English

This article was a review, presented at a 1993 workshop on chrysotile asbestos. It covered laboratory studies of how chrysotile affects cells in animals and in cell cultures, emphasizing studies published since 1985 and focusing on lung cancer and mesothelioma. The author cautioned that many studies lacked dose-response designs and suitable comparison dusts, and used poorly characterized fibre samples. The reviewed studies suggested that chrysotile was less active than crocidolite when compared by fibre number, but equally or more active when compared by weight. Studies of human bronchial epithelial cells and lung fibroblasts showed no chromosomal aberrations indicative of cell transformation. The author questioned whether chromosome changes in such tests reflect cancer potential, since erionite caused none in one test and latex beads tested positive in human lymphocytes in another. Inhaled chrysotile caused transient, reversible signs of cell proliferation in mice and rats. In a hamster study, no tumours followed chrysotile or benzopyrene alone, but lung carcinomas occurred with both together (reported as 83%). The author suggested that prolonged cell proliferation may be another mechanism of carcinogenesis.

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 of laboratory (animal and cell culture) studies; paper read at a workshop
• Who was studied: Published experimental studies in animals (rats, mice, hamsters) and in rodent and human cells in culture, with emphasis on studies published since 1985
• Exposure: Chrysotile asbestos, compared in some studies with crocidolite, amosite, erionite and non-pathogenic control dusts (e.g. titanium dioxide, latex beads), and in combination with chemical carcinogens such as those in cigarette smoke
• Main results:
  • Across the reviewed rodent cell studies, chrysotile appeared less active than crocidolite when compared by fibre number
  • Compared by weight, chrysotile was generally as active as or more active than crocidolite in the reviewed studies
  • Reviewed studies of human bronchial epithelial cells (Kodama et al., 1993) and human lung fibroblasts (Verschaeve et al., 1985) showed no chromosomal aberrations indicative of cell transformation
  • The author questioned the relevance of chromosome tests in human cells: erionite caused no effect in one assay, and in human lymphocytes clinoptilite and latex beads also tested positive (Korkina et al., 1992)
  • After inhalation by mice and rats, chrysotile caused transient and reversible increases in tritiated thymidine incorporation (a sign of DNA synthesis) in respiratory tract cells (Brody and Overby, 1989)
  • In rat pleural mesothelial cells, crocidolite and chrysotile caused persistent expression of the c-fos and c-jun genes, with a no-observed-effect level at the lowest doses; crocidolite was more potent per fibre
  • In hamsters, no tumours followed instillation of chrysotile or benzopyrene (BaP) alone, but lung carcinomas occurred when the two were applied together (83%)
  • In rats, chrysotile alone produced one tumour in 31 rats, while chrysotile combined with N-bis(hydroxypropyl)nitrosamine produced 23 tumours in 38 rats
• The authors' conclusion: The article text has no separate conclusion section. The author suggested that protracted cell proliferation by asbestos fibres over the long latency of disease may be another mechanism of carcinogenesis.
• Limitations the authors state:
  • The author noted that the reviewed literature lacks dose-response studies, both in animals and in cell cultures
  • The author noted that fibre samples used in experiments are poorly characterized physically and chemically
  • The author noted that it is unclear whether the mutagenicity findings with chrysotile reflect carcinogenicity or cytotoxicity, because control dusts were not used

Topics

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

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Chrysotile, Lung Cancer, Dose-response relationship, Mesothelioma, Mesothelial Cells, Crocidolite, Amosite.

Related studies

• Lung mesothelial cell and fibroblast responses to pleural and alveolar macrophage supernatants and to lavage fluids from crocidolite-exposed rats — I.Y. Adamson, H. Prieditis, et al. (1997)
• Lung proliferative and clearance responses to inhaled para-aramid RFP in exposed hamsters and rats: comparisons with chrysotile asbestos fibers — D.B. Warheit, S.I. Snajdr, et al. (1997)
• Chrysotile and rock wool fibers induce chromosome aberrations and DNA damage in V79 lung fibroblast cells — Y. Cui, J. Ma, et al. (2018)
• Increased expression of epidermal growth factor receptor in rat pleural mesothelial cells correlates with carcinogenicity of mineral fibres — S.P. Faux, C.E. Houghton, 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)
• Patterns of c-fos and c-jun proto-oncogene expression, apoptosis, and proliferation in rat pleural mesothelial cells exposed to erionite or asbestos fibers — C.R. Timblin, G.D. Guthrie, et al. (1998)

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