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

• Published in: Journal of Toxicology and Environmental Health, Part A Part A, 2018-01, Vol.81 (4), p.60-79
• Main Authors: Yanamala, Naveena, Kisin, Elena R., Gutkin, Dmitriy W., Shurin, Michael R., Harper, Martin, Shvedova, Anna A.
• Format: Article
• Language: English
• Subjects: Animals; Asbestos; Asbestos, Amphibole - toxicity; Asbestos, Crocidolite - toxicity; Asbestosis; Calcium Compounds - toxicity; Cancer; Carcinogenesis; Carcinogens; Chemokines; Comparative analysis; Crocidolite; Cytokines; Exposure; Female; Fibers; Gene expression; Gene regulation; Health risks; Inflammation; Inflammation - chemically induced; Lung - drug effects; Lung - immunology; Lung - pathology; Lung cancer; Lung diseases; Mesothelioma; Mice; Mice, Inbred C57BL; Pathogenicity; Pathogens; Silicates - toxicity; Transcriptome - drug effects; Tremolite; Wollastonite; Zeolites - toxicity
• ISSN: 1528-7394; 1087-2620; 2381-3504
• DOI: 10.1080/15287394.2017.1408201

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.