{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:17:54Z","timestamp":1780431474126,"version":"3.54.1"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"2","funder":[{"DOI":"10.13039\/100000125","name":"National Institute for Occupational Safety and Health","doi-asserted-by":"publisher","award":["939050Z"],"award-info":[{"award-number":["939050Z"]}],"id":[{"id":"10.13039\/100000125","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Smoking may modify the lung response to silica exposure including cancer and silicosis. Nevertheless, the precise role of exposure to tobacco smoke (TS) on the lung response to crystalline silica (CS) exposure and the underlying mechanisms need further clarification. The objectives of the present study were to determine the role of TS on lung response to CS exposure and the underlying mechanism(s). Male Fischer 344 rats were exposed by inhalation to air, CS (15\u2009mg\/m3, 6\u2009h\/day, 5\u2009days), TS (80\u2009mg\/m3, 3\u2009h\/day, twice weekly, 6\u2009months), or CS (15\u2009mg\/m3, 6\u2009h\/day, 5\u2009days) followed by TS (80\u2009mg\/m3, 3\u2009h\/day, twice weekly, 6\u2009months). The rats were euthanized 6\u2009months and 3\u2009weeks following initiation of the first exposure and the lung response was assessed. Silica exposure resulted in significant lung toxicity as evidenced by lung histological changes, enhanced neutrophil infiltration, increased lactate dehydrogenase levels, enhanced oxidant production, and increased cytokine levels. The TS exposure alone had only a minimal effect on these toxicity parameters. However, the combined exposure to TS and CS exacerbated the lung response, compared with TS or CS exposure alone. Global gene expression changes in the lungs correlated with the lung toxicity severity. Bioinformatic analysis of the gene expression data demonstrated significant enrichment in functions, pathways, and networks relevant to the response to CS exposure which correlated with the lung toxicity detected. Collectively our data demonstrated an exacerbation of CS-induced lung toxicity by TS exposure and the molecular mechanisms underlying the exacerbated toxicity.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaa146","type":"journal-article","created":{"date-parts":[[2020,9,11]],"date-time":"2020-09-11T03:45:34Z","timestamp":1599795934000},"page":"375-390","source":"Crossref","is-referenced-by-count":23,"title":["Tobacco Smoke Exposure Exacerbated Crystalline Silica-Induced Lung Toxicity in Rats"],"prefix":"10.1093","volume":"178","author":[{"given":"Tina M","family":"Sager","sequence":"first","affiliation":[{"name":"Health Effects Laboratory Division, National Institute for Occupational Safety and Health (NIOSH), Morgantown, West Virginia 26505"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina M","family":"Umbright","sequence":"additional","affiliation":[{"name":"Health Effects Laboratory Division, National Institute for Occupational Safety and Health (NIOSH), Morgantown, West Virginia 26505"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gul Mehnaz","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Health Effects Laboratory Division, National Institute for Occupational Safety and Health (NIOSH), Morgantown, West Virginia 26505"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveena","family":"Yanamala","sequence":"additional","affiliation":[{"name":"Health Effects Laboratory Division, National Institute for Occupational Safety and Health (NIOSH), Morgantown, West Virginia 26505"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard D","family":"Leonard","sequence":"additional","affiliation":[{"name":"Health Effects Laboratory Division, National Institute for Occupational Safety and Health (NIOSH), Morgantown, West Virginia 26505"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter G","family":"McKinney","sequence":"additional","affiliation":[{"name":"Health Effects Laboratory Division, National Institute for Occupational Safety and Health (NIOSH), Morgantown, West Virginia 26505"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L","family":"Kashon","sequence":"additional","affiliation":[{"name":"Health Effects Laboratory Division, National Institute for Occupational Safety and Health (NIOSH), Morgantown, West Virginia 26505"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pius","family":"Joseph","sequence":"additional","affiliation":[{"name":"Health Effects Laboratory Division, National Institute for Occupational Safety and Health (NIOSH), Morgantown, West Virginia 26505"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,25]]},"reference":[{"key":"2021012307302627500_kfaa146-B1","doi-asserted-by":"crossref","first-page":"R10","DOI":"10.1186\/ar4140","article-title":"Estradiol promotes the development of a fibrotic phenotype and is increased in the serum of patients with systemic sclerosis","volume":"15","author":"Aida-Yasuoka","year":"2013","journal-title":"Arthritis Res. 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