Characterization of pulmonary responses in mice to asbestos/asbestiform fibers using gene expression profiles

Our plain-English summary of Characterization of pulmonary responses in mice to asbestos/asbestiform fibers using gene expression profiles, by N. Yanamala, E.R. Kisin, D.W. Gutkin, et al (Journal of Toxicology and Environmental Health. Part a, 2018).

The study

• Authors: N. Yanamala, E.R. Kisin, D.W. Gutkin, M.R. Shurin, M. Harper, A.A. Shvedova
• Journal: Journal of Toxicology and Environmental Health. Part a
• Published: 2018;81(4):60-79
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Humans exposed to asbestos and/or asbestiform fibers are at high risk of developing many lung diseases including asbestosis, lung cancer, and malignant mesothelioma. However, the disease-causing potential and specific metabolic mechanisms and pathways associated with various asbestos/asbestiform fiber exposures triggering different carcinogenic and non-carcinogenic outcomes are still largely unknown. The aim of this this study was to investigate gene expression profiles and inflammatory responses to different asbestos/asbestiform fibers at the acute/sub-acute phase that may be related to delayed pathological outcomes observed at later time points. Mice were exposed to asbestos (crocidolite, tremolite asbestos), asbestiform fibers (erionite), and a low pathogenicity mineral fiber (wollastonite) using oropharyngeal aspiration. Similarities in inflammatory and tissue damage responses, albeit with quantitative differences, were observed at day 1 and 7 post treatment. Exposure to different fibers induced significant changes in regulation and release of a number of inflammatory cytokines/chemokines. Comparative analysis of changes in gene regulation in the lung on day 7 post exposure were interpretable in the context of differential biological responses that were consistent with histopathological findings at days 7 and 56 post treatment. Our results noted differences in the magnitudes of pulmonary responses and gene regulation consistent with pathological alterations induced by exposures to four asbestos/asbestiform fibers examined. Further comparative mechanistic studies linking early responses with the long-term endpoints may be instrumental to understanding triggering mechanisms underlying pulmonary carcinogenesis, that is lung cancer versus mesothelioma.

In plain English

This was an animal experiment. Female C57BL/6J mice had 80 μg of one of four mineral fibers placed into their lungs by pharyngeal aspiration. The fibers were crocidolite, tremolite asbestos, erionite (an asbestiform mineral from Rome, Oregon), or wollastonite, which the authors describe as a low-pathogenicity fiber. Control mice received saline. The authors measured inflammation, tissue damage and signalling molecules at 1 and 7 days, gene activity at 7 days, and tissue changes at 7 and 56 days. Crocidolite, tremolite asbestos and erionite raised a marker of tissue damage on days 1 and 7. Significantly changed genes numbered 1716 for crocidolite, 413 for tremolite asbestos, 133 for wollastonite and 78 for erionite. Tissue changes were most severe with crocidolite (equal to or greater than tremolite asbestos), then erionite, then wollastonite. Erionite caused inflammation and, by 56 days, fibrosis, but no granulomas; its gene changes suggested possible disease-causing responses that tissue sections did not show. The authors concluded that, at equal mass, crocidolite and then tremolite asbestos were the most pathologically active. They called for longer studies that match fiber numbers and size distributions.

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: Animal experiment: mice given a single dose of fibers into the lungs by pharyngeal aspiration, compared with saline-treated controls; follow-up at 1, 7 and 56 days
• Who was studied: Female C57BL/6J mice aged 8–9 weeks, purchased from Jackson Laboratories
• Exposure: 80 μg per mouse of crocidolite (UICC sample), tremolite asbestos (Lone Pine, California), erionite (Rome, Oregon) or wollastonite (Hubei, China)
• Main results:
  • Total cells in lung lavage fluid were significantly increased on day 7 in mice given crocidolite, tremolite asbestos and erionite
  • LDH activity, a tissue damage marker, was significantly raised on days 1 and 7 in mice given crocidolite, tremolite asbestos and erionite
  • The chemokine Rantes was significantly raised only in erionite-exposed mice
  • At day 7, the number of genes with a significant change of at least 2.5-fold was 78 for erionite, 1716 for crocidolite, 413 for tremolite asbestos and 133 for wollastonite
  • Severity of lung tissue changes was in the order crocidolite equal to or greater than tremolite asbestos, then erionite, then wollastonite
  • At 56 days, erionite-exposed lungs showed mild chronic peribronchial and perivascular inflammation, mild to moderate lymphocytic infiltration and fibrosis, and no granulomas
  • Wollastonite caused no detectable inflammation, hyperplasia or fibrosis at day 7. At 56 days some mice had mild perivascular inflammation and fibrosis
  • For erionite, gene analysis suggested possible pathogenic or carcinogenic responses, but tissue sections did not show such manifestations
• The authors' conclusion: The authors concluded that, at an equal mass dose, crocidolite and then tremolite asbestos were more pathologically active than the other fibers tested
• Limitations the authors state:
  • The milder findings with erionite may reflect that more time is needed for disease to develop, so longer studies are required
  • Fibers were dosed by equal mass, and the total number of fibers was lower for erionite and wollastonite than for the asbestos samples
  • The authors called for future long-duration studies that correct for identical fiber numbers and size distributions

Topics

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

Medical terms in this study, explained in our Lexicon: Asbestiform, Lung Cancer, Malignant Mesothelioma, Carcinogenic, Crocidolite, Tremolite, erionite, Mineral Fiber.

Related studies

• Production of reactive oxygen species by phagocytic cells after exposure to glass wool and stone wool fibres - effect of fibre preincubation in aqueous solution — T. Zoller, W.J. Zeller (2000)
• Mesothelial cell proliferation and biopersistence of wollastonite and crocidolite asbestos fibers — J.L. Macdonald, A.B. Kane (1997)
• Investigation on the durability of man-made vitreous fibers in rat lungs — B. Bellmann, H. Muhle, et al. (1994)
• Pulmonary toxicity of wollastonite in vivo and in vitro — E. Tátrai, Z. Kováciková, et al. (2004)
• Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study — B.N. Snyder-Talkington, C. Dong, et al. (2016)
• Assessments of lung digestion methods for recovery of fibers — D.B. Warheit, H.C. Hwang, et al. (1991)

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