{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:52:21Z","timestamp":1772160741252,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Nitric oxide is an important regulator of the epigenetic landscape of cellular homeostatic and pathological states, in which post\u2010translational modifications of the epigenome\u2010modulating enzymes are the most well described mechanism. Considering that alterations of the histone acetylation pattern were associated with oral cancer development and progression, the purpose of this study was to analyze the immunohistochemical expression of H3K9ac and H3K27ac at different stages of oral carcinogenesis induced by 4\u2010nitroquinoline\u2010\n                      <jats:italic>N<\/jats:italic>\n                      \u2010oxide (4NQO) in Nos2\n                      <jats:sup>+\/+<\/jats:sup>\n                      (wild\u2010type) and Nos2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      (knockout) mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      C57BL\/6J and B6.129P2\u2010Nos2\n                      <jats:sup>tm1Lau<\/jats:sup>\n                      \/J mice were treated with 4NQO in the drinking water at 50\u2009\u03bcg\/mL for 16\u2009weeks and observed for 8\u2009weeks. Tongues were submitted to histopathological analysis and immunohistochemistry for H3K9ac and H3K27ac expression. The antigen\u2013antibody reaction was analyzed with quickscore (QS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both histone acetylation marks were expressed in the normal epithelium. QS values were higher in moderate dysplasia of Nos2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.025) when compared to Nos2\n                      <jats:sup>+\/+<\/jats:sup>\n                      , and mild dysplasia had lower values for H3K9ac when compared to moderate and severe dysplasia in the Nos2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.015). H3K27ac significantly increased from normal mucosa to mild dysplasia in Nos2\n                      <jats:sup>+\/+<\/jats:sup>\n                      mice (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007). Additionally, Nos2\n                      <jats:sup>+\/+<\/jats:sup>\n                      mice had a higher number of H3K27ac\u2010positive mild dysplasias when compared to Nos2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      (\n                      <jats:italic>p\u2009=<\/jats:italic>\n                      \u20090.023).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The pattern of histone acetylation changes in murine oral carcinogenesis, mainly when the epithelial lining of the tongue becomes dysplastic, and such epigenetic modifications might be iNOS\u2010mediated.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jop.70021","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T09:51:43Z","timestamp":1754473903000},"page":"715-722","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunohistochemical Expression of\n                    <scp>H3K9ac<\/scp>\n                    and\n                    <scp>H3K27ac<\/scp>\n                    in Premalignant and Malignant Tongue Lesions of Wild\u2010Type and Nos2\u2010Knockout Mice Treated With\n                    <scp>4NQO<\/scp>"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7560-6531","authenticated-orcid":false,"given":"Ana\u00edra Ribeiro Guedes Fonseca","family":"Costa","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Pathology Federal University of Uberl\u00e2ndia  Uberl\u00e2ndia 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