Anaíra Ribeiro Guedes Fonseca Costa, Débora de Oliveira de Santos, Mariana Daiani Costa Silva, Ianca Daniele Oliveira de Jesus, Lúbia Cristina Fonseca, Sérgio Vitorino Cardoso, Paulo Rogério de Faria, Adriano Mota Loyola
{"title":"H3K9ac和H3K27ac在野生型和nos2基因敲除小鼠舌癌前和舌癌中的免疫组化表达","authors":"Anaíra Ribeiro Guedes Fonseca Costa, Débora de Oliveira de Santos, Mariana Daiani Costa Silva, Ianca Daniele Oliveira de Jesus, Lúbia Cristina Fonseca, Sérgio Vitorino Cardoso, Paulo Rogério de Faria, Adriano Mota Loyola","doi":"10.1111/jop.70021","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Nitric oxide is an important regulator of the epigenetic landscape of cellular homeostatic and pathological states, in which post-translational modifications of the epigenome-modulating 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-nitroquinoline-<i>N</i>-oxide (4NQO) in Nos2<sup>+/+</sup> (wild-type) and Nos2<sup>−/−</sup> (knockout) mice.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>C57BL/6J and B6.129P2-Nos2<sup>tm1Lau</sup>/J mice were treated with 4NQO in the drinking water at 50 μg/mL for 16 weeks and observed for 8 weeks. Tongues were submitted to histopathological analysis and immunohistochemistry for H3K9ac and H3K27ac expression. The antigen–antibody reaction was analyzed with quickscore (QS).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Both histone acetylation marks were expressed in the normal epithelium. QS values were higher in moderate dysplasia of Nos2<sup>−/−</sup> mice (<i>p</i> = 0.025) when compared to Nos2<sup>+/+</sup>, and mild dysplasia had lower values for H3K9ac when compared to moderate and severe dysplasia in the Nos2<sup>−/−</sup> group (<i>p</i> = 0.015). H3K27ac significantly increased from normal mucosa to mild dysplasia in Nos2<sup>+/+</sup> mice (<i>p</i> = 0.007). Additionally, Nos2<sup>+/+</sup> mice had a higher number of H3K27ac-positive mild dysplasias when compared to Nos2<sup>−/−</sup> (<i>p =</i> 0.023).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <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-mediated.</p>\n </section>\n </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"54 8","pages":"715-722"},"PeriodicalIF":2.3000,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Immunohistochemical Expression of H3K9ac and H3K27ac in Premalignant and Malignant Tongue Lesions of Wild-Type and Nos2-Knockout Mice Treated With 4NQO\",\"authors\":\"Anaíra Ribeiro Guedes Fonseca Costa, Débora de Oliveira de Santos, Mariana Daiani Costa Silva, Ianca Daniele Oliveira de Jesus, Lúbia Cristina Fonseca, Sérgio Vitorino Cardoso, Paulo Rogério de Faria, Adriano Mota Loyola\",\"doi\":\"10.1111/jop.70021\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Nitric oxide is an important regulator of the epigenetic landscape of cellular homeostatic and pathological states, in which post-translational modifications of the epigenome-modulating 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-nitroquinoline-<i>N</i>-oxide (4NQO) in Nos2<sup>+/+</sup> (wild-type) and Nos2<sup>−/−</sup> (knockout) mice.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>C57BL/6J and B6.129P2-Nos2<sup>tm1Lau</sup>/J mice were treated with 4NQO in the drinking water at 50 μg/mL for 16 weeks and observed for 8 weeks. Tongues were submitted to histopathological analysis and immunohistochemistry for H3K9ac and H3K27ac expression. The antigen–antibody reaction was analyzed with quickscore (QS).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Both histone acetylation marks were expressed in the normal epithelium. QS values were higher in moderate dysplasia of Nos2<sup>−/−</sup> mice (<i>p</i> = 0.025) when compared to Nos2<sup>+/+</sup>, and mild dysplasia had lower values for H3K9ac when compared to moderate and severe dysplasia in the Nos2<sup>−/−</sup> group (<i>p</i> = 0.015). H3K27ac significantly increased from normal mucosa to mild dysplasia in Nos2<sup>+/+</sup> mice (<i>p</i> = 0.007). Additionally, Nos2<sup>+/+</sup> mice had a higher number of H3K27ac-positive mild dysplasias when compared to Nos2<sup>−/−</sup> (<i>p =</i> 0.023).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <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-mediated.</p>\\n </section>\\n </div>\",\"PeriodicalId\":16588,\"journal\":{\"name\":\"Journal of Oral Pathology & Medicine\",\"volume\":\"54 8\",\"pages\":\"715-722\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-08-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Oral Pathology & Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/jop.70021\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Oral Pathology & Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jop.70021","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
Immunohistochemical Expression of H3K9ac and H3K27ac in Premalignant and Malignant Tongue Lesions of Wild-Type and Nos2-Knockout Mice Treated With 4NQO
Background
Nitric oxide is an important regulator of the epigenetic landscape of cellular homeostatic and pathological states, in which post-translational modifications of the epigenome-modulating 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-nitroquinoline-N-oxide (4NQO) in Nos2+/+ (wild-type) and Nos2−/− (knockout) mice.
Methods
C57BL/6J and B6.129P2-Nos2tm1Lau/J mice were treated with 4NQO in the drinking water at 50 μg/mL for 16 weeks and observed for 8 weeks. Tongues were submitted to histopathological analysis and immunohistochemistry for H3K9ac and H3K27ac expression. The antigen–antibody reaction was analyzed with quickscore (QS).
Results
Both histone acetylation marks were expressed in the normal epithelium. QS values were higher in moderate dysplasia of Nos2−/− mice (p = 0.025) when compared to Nos2+/+, and mild dysplasia had lower values for H3K9ac when compared to moderate and severe dysplasia in the Nos2−/− group (p = 0.015). H3K27ac significantly increased from normal mucosa to mild dysplasia in Nos2+/+ mice (p = 0.007). Additionally, Nos2+/+ mice had a higher number of H3K27ac-positive mild dysplasias when compared to Nos2−/− (p = 0.023).
Conclusion
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-mediated.
期刊介绍：
The aim of the Journal of Oral Pathology & Medicine is to publish manuscripts of high scientific quality representing original clinical, diagnostic or experimental work in oral pathology and oral medicine. Papers advancing the science or practice of these disciplines will be welcomed, especially those which bring new knowledge and observations from the application of techniques within the spheres of light and electron microscopy, tissue and organ culture, immunology, histochemistry and immunocytochemistry, microbiology, genetics and biochemistry.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
