Characterization of Pulmonary Responses in Mice to Asbestos/Asbestiform Fibers Using Gene Expression Profiles
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2018/03/01
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Description: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 related processes associated with various asbestos/asbestiform fiber exposures in triggering the different (non-)carcinogenic outcomes is still largely unknown. In this study, we investigated whether exposure to different asbestos/asbestiform fibers leads to differences in inflammatory responses and gene expression profiles at acute/subacute phases that can be related to pathological outcomes observed at extended time points of post-exposure. We exposed mice to asbestos (crocidolite, tremolite asbestos), asbestiform fibers (erionite), and a low-pathogenicity mineral fiber (wollastonite) using oropharyngeal aspiration. We observed some shared inflammatory and tissue damage responses, albeit to different extents, at day 1 and 7 post-exposure. In addition, exposure to different fibers also exhibited distinct changes in the regulation and release of a number of inflammatory mediators. Further, a detailed comparison of gene regulation changes in the lungs on day 7 post-exposure also suggested differential biological responses that were consistent with histopathological changes at day 7 and 56 post-exposure. Taken together, these results suggest clear differences in the magnitude of various pulmonary responses and gene regulation that were consistent with pathological alterations upon exposure to the four asbestos/asbestiform fibers studied. Further mechanistic studies focusing on long-term endpoints are critical for understanding how early biological responses are associated with pulmonary exposures to asbestos/asbestiform materials and their ability in triggering different carcinogenic outcomes, i.e., lung cancer versus mesothelioma. [Description provided by NIOSH]
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ISSN:1096-6080
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Pages in Document:44
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Volume:162
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Issue:1
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NIOSHTIC Number:nn:20051140
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Citation:Toxicologist 2018 Mar; 162(1):44
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Federal Fiscal Year:2018
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Peer Reviewed:False
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Source Full Name:The Toxicologist. Society of Toxicology 57th Annual Meeting and ToxExpo, March 11-15, 2018, San Antonio, Texas
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Main Document Checksum:urn:sha-512:69c8169c4e208742ee4452f979c0e77d90a183e40a5ef1de5b223be40d202eb8968daafcbd09071989c4a74671df4c9e232ebd6da72b65177cf9ddf056a6a1dd
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