{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:21:05Z","timestamp":1790857265852,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec><jats:title>Objectives\/Hypothesis<\/jats:title><jats:p>We recently documented that acidic bile, a gastroesophageal reflux content, can cause invasive hypopharyngeal squamous cell carcinoma, by inducing widespread DNA damage and promoting nuclear factor kappa B (NF\u2010\u03baB)\u2010related oncogenic molecular events. Poly or adenosine diphosphate (ADP)\u2010ribose polymerase\u20101 (PARP\u20101), a sensitive sensor of DNA damage, may interact with NF\u2010\u03baB. We hypothesized that PARP\u20101 is activated in hypopharyngeal cells (HCs) with marked DNA damage caused by acidic bile, hence there is an association between PARP\u20101 and NF\u2010\u03baB activation or its related oncogenic profile, in this process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>In vitro study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We targeted PARP\u20101 and NF\u2010\u03baB(p65), using pharmacologic inhibitors, 1.0\u2009\u03bcM Rucaparib (AG014699) and 10\u2009\u03bcM BAY 11\u20137082 {3\u2010[4=methylphenyl)sulfonyl]\u2010(2E)\u2010propenenitrile}, respectively, or silencing their gene expression (siRNAs) and used immunofluorescence, luciferase, cell viability, direct enzyme\u2010linked immunosorbent assays, and qPCR analysis to detect the effect of targeting PARP\u20101 or NF\u2010\u03baB in acidic bile\u2010induced DNA damage, PARP\u20101, p\u2010NF\u2010\u03baB, and B\u2010cell lymphoma 2 (Bcl\u20102) expression, as well as NF\u2010\u03baB transcriptional activity, cell survival, and mRNA oncogenic phenotype in HCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We showed that (i) PARP\u20101 is overexpressed by acidic bile, (ii) targeting NF\u2010\u03baB adequately prevents the acidic bile\u2010induced DNA double\u2010strand breaks (DSBs) by gamma H2A histone family member X (\u03b3H2AX), oxidative DNA\/RNA damage, PARP\u20101 overexpression, anti\u2010apoptotic mRNA phenotype, and cell survival, whereas (iii) targeting PARP\u20101 preserves elevated DNA damage, NF\u2010\u03baB activation, and anti\u2010apoptotic phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We document for the first time that the activation of PARP\u20101 is an early event during bile reflux\u2010related head and neck carcinogenesis and that NF\u2010\u03baB can mediate DNA damage and PARP\u20101 activation. Our data encourage further investigation into how acidic bile\u2010induced activated NF\u2010\u03baB mediates DNA damage in hypopharyngeal carcinogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 133:1146\u20131155, 2023<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.30284","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T11:28:52Z","timestamp":1657106932000},"page":"1146-1155","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Role of <scp>PARP<\/scp>\u20101 and <scp>NF\u2010\u03baB<\/scp> in <scp>Bile\u2010Induced DNA<\/scp> Damage and Oncogenic Profile in Hypopharyngeal Cells"],"prefix":"10.1002","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8050-963X","authenticated-orcid":false,"given":"Panagiotis G.","family":"Doukas","sequence":"first","affiliation":[{"name":"The Yale 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