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A recent 2-year National Toxicology Program carcinogenicity bioassay showed that male F344\/N rats exposed to the industrial toxicant vinylidene chloride (VDC) resulted in a marked increase in malignant mesothelioma. Global gene expression profiles of these tumors were compared to spontaneous mesotheliomas and the F344\/N rat mesothelial cell line (Fred-PE) in order to characterize the molecular features and chemical-specific profiles of mesothelioma in VDC-exposed rats. As expected, mesotheliomas from control and VDC-exposed rats shared pathways associated with tumorigenesis, including cellular and tissue development, organismal injury, embryonic development, inflammatory response, cell cycle regulation, and cellular growth and proliferation, while mesotheliomas from VDC-exposed rats alone showed overrepresentation of pathways associated with pro-inflammatory pathways and immune dysfunction such as the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, interleukin (IL)-8 and IL-12 signaling, interleukin responses, Fc receptor signaling, and natural killer and dendritic cells signaling, as well as overrepresentation of DNA damage and repair. These data suggest that a chronic, pro-inflammatory environment associated with VDC exposure may exacerbate disturbances in oncogene, growth factor, and cell cycle regulation, resulting in an increased incidence of mesothelioma.<\/jats:p>","DOI":"10.1177\/0192623314537885","type":"journal-article","created":{"date-parts":[[2014,6,24]],"date-time":"2014-06-24T01:08:05Z","timestamp":1403572085000},"page":"171-185","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Gene Expression of Mesothelioma in Vinylidene Chloride\u2013exposed F344\/N Rats Reveal Immune Dysfunction, Tissue Damage, and Inflammation Pathways"],"prefix":"10.1177","volume":"43","author":[{"given":"Pamela E.","family":"Blackshear","sequence":"first","affiliation":[{"name":"Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA"},{"name":"Integrated Laboratory 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