Multiple mechanisms for the carcinogenic effects of asbestos and other mineral fibers

Our plain-English summary of Multiple mechanisms for the carcinogenic effects of asbestos and other mineral fibers, by J.C. Barrett, P.W. Lamb, R.W. Wiseman (Environmental Health Perspectives, 1989).

The study

• Authors: J.C. Barrett, P.W. Lamb, R.W. Wiseman
• Journal: Environmental Health Perspectives
• Published: 1989;81:81-9
• Type of article: Review
• Cited by: 87 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 005000).

Abstract

Asbestos and other mineral fibers are carcinogenic to humans and animals but differ from many carcinogens in that they do not induce gene mutations. An understanding of these interesting human carcinogens, therefore, is an important problem in cancer research. Asbestos and other fibers induce predominantly two types of cancers: mesotheliomas and bronchogenic carcinomas. Fiber size is an important factor in the carcinogenic activity of these substances as has been shown for mesothelioma induction. For bronchogenic carcinomas, but not for mesotheliomas, a synergistic effect of asbestos exposure and cigarette smoke has been observed in humans. The mechanisms by which fibers alone versus fibers in concert with other carcinogens induce cancers are probably distinct. In addition to fiber dimensions, fiber durability and surface properties of fibers are important properties affecting carcinogenicity. Evidence exists that asbestos is a complete carcinogen, an initiator and a promoter. Multiple mechanisms must be operative to explain the diverse effects of mineral fibers. Although asbestos is inactive as a gene mutagen, there is now clear evidence that it induces chromosomal mutations (aneuploidy and aberrations) in a wide variety of mammalian cells including mesothelial cells. Asbestos also induces transformation of cells in culture including mesothelial cells and fibroblasts. A mechanism for cell transformation, which is dependent on fiber dimension, has been proposed. The fibers are phagocytized by the cells and accumulate in the perinuclear region of the cells. When the cell undergoes mitosis, the physical presence of the fibers interferes with chromosome segregation and results in anaphase abnormalities. The transformed cells show aneuploidy and other chromosome abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

This article was a review by the authors of how asbestos and other mineral fibers may cause cancer. It drew on published work by others and on experiments from the authors' own laboratory. In the laboratory's earlier work with Syrian hamster embryo cells grown in culture, chrysotile and crocidolite asbestos caused dose-dependent transformation of the cells but did not cause gene mutations at the two genetic sites tested. Glass fibers lost their transforming ability when milling shortened them from an average of 16.0 to 0.95 micrometres. Asbestos fibers were taken up by the cells within 24 hours and gathered around the nucleus. Chrysotile-exposed cells showed a large increase in abnormal chromosome separation during cell division. In a separate experiment, DNA from three human mesotheliomas was transferred into a mouse cell line (NIH 3T3). Those cells formed tumors in nude mice between 7 and 14 weeks, and the authors reported that the transforming genes involved were not ras genes. The review also described other researchers' findings of chromosome 3 deletions in human mesotheliomas. The authors concluded that the fibers are likely to act by multiple mechanisms. In their view, the fibers do not induce gene mutations but do induce chromosomal changes that may affect cancer-related genes.

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 asbestos carcinogenesis mechanisms, combining published studies by others with experiments from the authors' own laboratory (cell culture and gene transfer experiments)
• Who was studied: Early passage, diploid Syrian hamster embryo cells in culture (laboratory experiments). Separately, DNA from three human mesotheliomas, transferred into NIH 3T3 cells that were then injected into nude mice
• Exposure: Chrysotile and crocidolite asbestos, Code 100 glass fibers (unmilled and milled), and alpha quartz applied to cells in culture. Benzo[a]pyrene was used as a comparison carcinogen
• Main results:
  • In Syrian hamster embryo cells, chrysotile and crocidolite asbestos induced dose-dependent morphological and neoplastic transformation but failed to induce gene mutations at two specific genetic loci
  • Milling shortened glass fibers from 16.0 to 0.95 micrometres in average length, with average diameter unchanged. Milling completely eliminated the transforming ability of the glass fibers in hamster cells
  • Asbestos fibers were taken up by the hamster cells by phagocytosis within 24 hours and accumulated around the nucleus 24 to 48 hours after exposure
  • Chrysotile-exposed hamster cells showed a large increase in cells with anaphase abnormalities (lagging chromosomes, bridges, sticky chromosomes). The authors proposed that the fibers physically interfere with chromosome segregation, resulting in aneuploidy
  • Activated H-ras oncogenes were present in approximately 50% of asbestos-induced hamster tumor-derived cell lines and absent from nontumorigenic immortalized lines. The authors interpreted this H-ras mutation as a secondary, spontaneous change rather than a direct result of asbestos
  • NIH 3T3 cultures given DNA from human mesotheliomas formed tumors in nude mice between 7 and 14 weeks. Cultures given normal DNA were nontumorigenic for up to 16 weeks. No new H-ras, K-ras or N-ras sequences were found, and the authors concluded that the transforming genes are not members of the ras family
• The authors' conclusion: The authors concluded that asbestos and other mineral fibers induce multiple types of cancers and are likely to act by multiple mechanisms. In their view, the fibers do not induce gene mutations but are active inducers of chromosomal changes, which may affect protooncogenes or tumor suppressor genes.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenic, Mineral Fiber, Mesothelioma, Bronchogenic Carcinoma, Synergistic Effect, Asbestos Exposure, Fiber Dimensions, Fiber Durability.

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