Characterization of pulmonary responses in mice to asbestos/asbestiform fibers using gene expression profiles. Issue 4 (16th February 2018)

• Record Type: Journal Article
• Authors: Yanamala, Naveena; Kisin, Elena R.; Gutkin, Dmitriy W.; Shurin, Michael R.; Harper, Martin; Shvedova, Anna A.
• Is Part Of: Journal of toxicology and environmental health. Volume 81:Issue 4(2018)
• Page Start: 60
• Page End: 79
• Publication Date: 2018-02-16
• Subjects: Toxicology -- Periodicals; Environmental health -- Periodicals; 615.90205
• DOI: 10.1080/15287394.2017.1408201
• Languages: English
• ISSNs: 1528-7394

Abstract

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.