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

J Toxicol Environ Health A. 2018;81(4):60-79. doi: 10.1080/15287394.2017.1408201. Epub 2017 Dec 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asbestos, Amphibole / toxicity*
  • Asbestos, Crocidolite / toxicity*
  • Calcium Compounds / toxicity*
  • Female
  • Inflammation / chemically induced
  • Lung / drug effects*
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Silicates / toxicity*
  • Transcriptome / drug effects*
  • Zeolites / toxicity*


  • Asbestos, Amphibole
  • Calcium Compounds
  • Silicates
  • Asbestos, Crocidolite
  • erionite
  • Zeolites
  • tremolite
  • calcium silicate