{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:18:01Z","timestamp":1792783081210,"version":"4.5.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universidade Federal Do Rio Grande Do Norte","id":[{"id":"https:\/\/ror.org\/04wn09761","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Histol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Given the scarcity of experimental studies on the effects of induced oral carcinogenesis on the minor salivary glands, the aim of this study was to analyze the histopathological changes present in the lingual and palatal minor salivary glands (MiSGs) resulting from 4NQO exposure in rats from the 8th to the 30th week of the experiment. Eleven rats were used in the control group and 45 rats in the experimental groups that received 4NQO\/propylene glycol diluted in drinking water. Histopathological analysis revealed evidence of hyperplasia, metaplasia, and ductal dysplasia, saliva buildup in the ducts, inflammatory infiltrate, lobular atrophy, degeneration of the secretory portion, fibrosis\/replacement, and invasion of the minor salivary glands. The most evident change in both tongue and palate MiSGs was degeneration of the secretory portion, which reduced salivation and promoted the oncogenic action of 4NQO. However, changes such as hyperplasia, metaplasia, and dysplasia, which may promote the development of neoplastic changes, were more prevalent in tongue MiSGs. In the present study, we also identified an incidental case of salivary ductal carcinoma in palatal MiSGs. Given this, it is important to be vigilant regarding potential changes in MiSGs, as they may be related to the development of malignancies.<\/jats:p>","DOI":"10.1007\/s10735-026-10938-5","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:21:29Z","timestamp":1787718089000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Changes in the minor salivary glands and ductal carcinoma resulting from induction of oral carcinogenesis"],"prefix":"10.1007","volume":"57","author":[{"given":"Caio Rodrigues","family":"Maia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raissa Cl\u00e1udia Eufr\u00e1zio","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviane Tain\u00e1 Carvalho","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cec\u00edlia Cerqueira","family":"Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian Gracielly Nascimento","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alana Beatriz Brito","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Paulo","family":"de Andrade Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"issue":"8","key":"10938_CR1","doi-asserted-by":"publisher","first-page":"151451","DOI":"10.1016\/j.acthis.2019.151451","volume":"121","author":"DJ Aframian","year":"2019","unstructured":"Aframian DJ, Keshet N, Nadler C, Zadik Y, Vered M (2019) Minor salivary glands: clinical, histological and immunohistochemical features of common and less common pathologies. Acta Histochem 121(8):151451. https:\/\/doi.org\/10.1016\/j.acthis.2019.151451","journal-title":"Acta Histochem"},{"issue":"2","key":"10938_CR12","doi-asserted-by":"publisher","first-page":"299","DOI":"10.4103\/jcrt.jcrt_1832_21","volume":"19","author":"R Bhola","year":"2023","unstructured":"Bhola R, Narwal A, Kamboj M, Devi A, Anand R, Chatterjee S (2023) Histopathological evaluation of minor salivary gland aberrations in oral squamous cell carcinoma. J Cancer Res Ther 19(2):299\u2013303. https:\/\/doi.org\/10.4103\/jcrt.jcrt_1832_21","journal-title":"J Cancer Res Ther"},{"issue":"4","key":"10938_CR19","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1111\/his.15217","volume":"85","author":"MN Dababneh","year":"2024","unstructured":"Dababneh MN, Griffith CC, Magliocca KR, Stojanov IJ (2024) Salivary duct carcinoma with squamous differentiation: histomorphological and immunophenotypical analysis of six cases. Histopathology 85(4):590\u2013597. https:\/\/doi.org\/10.1111\/his.15217","journal-title":"Histopathology"},{"key":"10938_CR5","doi-asserted-by":"publisher","first-page":"1325161","DOI":"10.3389\/fimmu.2024.1325161","volume":"15","author":"J Das","year":"2024","unstructured":"Das J, Bera S, Ganguly N, Guha I, Ghosh Halder T, Bhuniya A, Nandi P, Chakravarti M, Dhar S, Sarkar A, Das T, Banerjee S, Ghose S, Bose A, Baral R (2024) The immunomodulatory impact of naturally derived neem leaf glycoprotein on the initiation progression model of 4NQO induced murine oral carcinogenesis: a preclinical study. Front Immunol 15:1325161. https:\/\/doi.org\/10.3389\/fimmu.2024.1325161","journal-title":"Front Immunol"},{"issue":"1","key":"10938_CR2","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1007\/s10735-024-10306-1","volume":"56","author":"FP de Moraes","year":"2025","unstructured":"de Moraes FP, Florezi GP, Hsieh R, Dos Santos CP, Andriolo F, Louren\u00e7o SV (2025) A morphological post mortem profile in minor salivary glands changes in females. J Mol Histol 56(1):32. https:\/\/doi.org\/10.1007\/s10735-024-10306-1","journal-title":"J Mol Histol"},{"key":"10938_CR11","first-page":"E315","volume":"11","author":"MC da Ferreira de Aguiar","year":"2006","unstructured":"Ferreira de Aguiar MC, Gomes Dos Reis D, da Silva Fonseca LM, Vitorino Cardoso S, Alvarez Leite J, Vieira do Carmo MA (2006) Immunohistochemical evaluation of metallothionein in palatal mucosal cells of mice treated with 4NQO. Med Oral Patol Oral Cir Bucal 11:E315\u2013318","journal-title":"Med Oral Patol Oral Cir Bucal"},{"issue":"4","key":"10938_CR13","first-page":"1124","volume":"12","author":"\u00d6 Gunhan","year":"2019","unstructured":"Gunhan \u00d6, K\u0131l\u0131nc M, Kahraman D, Aksoy S, Cicek AF, Celasun B (2019) Parenchymal changes of salivary glands adjacent to a variety of salivary gland disorders. Int J Clin Exp Pathol 12(4):1124\u20131133","journal-title":"Int J Clin Exp Pathol"},{"issue":"1","key":"10938_CR15","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1034\/j.1600-0714.2001.300108.x","volume":"30","author":"I Kaplan","year":"2001","unstructured":"Kaplan I, Engelberg J, Dayan D (2001) The effect of desalivation on 4-nitroquinoline-1-oxide-induced tongue carcinogenesis: a morphometric study of nucleolar organizer regions. J Oral Pathol Med 30(1):48\u201352. https:\/\/doi.org\/10.1034\/j.1600-0714.2001.300108.x","journal-title":"J Oral Pathol Med"},{"issue":"1","key":"10938_CR18","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1007\/s00405-021-06757-x","volume":"279","author":"K Luna-Ortiz","year":"2022","unstructured":"Luna-Ortiz K, Dominguez-Malagon H, Corredor-Alonso GE, Reynoso-Noveron N, Herrera-Ponzanelli C, Luna-Peteuil Z, Zacarias-Ramon LC (2022) Clinicopathological and immunohistochemical behavior of ductal carcinoma of the salivary and lacrimal gland in a Mexican Mestizo population. Eur Arch Otorhinolaryngol 279(1):327\u2013333. https:\/\/doi.org\/10.1007\/s00405-021-06757-x","journal-title":"Eur Arch Otorhinolaryngol"},{"issue":"7","key":"10938_CR3","doi-asserted-by":"publisher","first-page":"ZC12","DOI":"10.7860\/JCDR\/2016\/20218.8116","volume":"10","author":"SP Mohan","year":"2016","unstructured":"Mohan SP, Chitturi RT, Ragunathan YT, Lakshmi SJ, Nallusamy J, Joseph I (2016) Minor salivary gland changes in oral epithelial dysplasia and oral squamous cell carcinoma\u2014a histopathological study. J Clin Diagn Res 10(7):ZC12\u2013ZC15. https:\/\/doi.org\/10.7860\/JCDR\/2016\/20218.8116","journal-title":"J Clin Diagn Res"},{"issue":"4","key":"10938_CR20","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1007\/s12105-023-01587-1","volume":"17","author":"KJ Nielson","year":"2023","unstructured":"Nielson KJ, Lorenzo G, Agarwal S (2023) Salivary duct carcinoma arising in a warthin tumor of the parotid gland: a rare case report with review of literature and PD-L1 expression. Head Neck Pathol 17(4):1042\u20131051. https:\/\/doi.org\/10.1007\/s12105-023-01587-1","journal-title":"Head Neck Pathol"},{"issue":"8","key":"10938_CR8","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1080\/10520295.2021.1882699","volume":"96","author":"R Rodrigues Rodrigues","year":"2021","unstructured":"Rodrigues Rodrigues R, Maia de Queiroz MS, da Silveira \u00c9JD, Freitas RA, de Souza LB, de Andrade Santos PP (2021) Identification of elastofibroma and elastofibroma-like lesions in cases diagnosed as oral fibromas. Biotech Histochem 96(8):608\u2013615. https:\/\/doi.org\/10.1080\/10520295.2021.1882699","journal-title":"Biotech Histochem"},{"key":"10938_CR6","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/bs.mcb.2021.01.001","volume":"163","author":"SH Sagheer","year":"2021","unstructured":"Sagheer SH, Whitaker-Menezes D, Han JYS, Curry JM, Martinez-Outschoorn U, Philp NJ (2021) 4NQO induced carcinogenesis: a mouse model for oral squamous cell carcinoma. Methods Cell Biol 163:93\u2013111. https:\/\/doi.org\/10.1016\/bs.mcb.2021.01.001","journal-title":"Methods Cell Biol"},{"key":"10938_CR4","doi-asserted-by":"publisher","first-page":"1274519","DOI":"10.3389\/fimmu.2023.1274519","volume":"14","author":"SR Sahu","year":"2023","unstructured":"Sahu SR, Thakur S, Peroumal D, Utkalaja BG, Dutta A, Kumari P, Subhadarsini I, Acharya N (2023) 4-nitroquinoline 1-oxide induces immune cells death to onset early immunosuppression during oral squamous cell carcinoma development. Front Immunol 14:1274519. https:\/\/doi.org\/10.3389\/fimmu.2023.1274519","journal-title":"Front Immunol"},{"key":"10938_CR17","doi-asserted-by":"publisher","first-page":"105525","DOI":"10.1016\/j.oraloncology.2021.105525","volume":"122","author":"SC Sarode","year":"2021","unstructured":"Sarode SC, Sarode GS, Sengupta N, Ghone U (2021) Tobacco induced epithelial dysplasia at minor salivary gland excretory duct and oral cancer. Oral Oncol 122:105525. https:\/\/doi.org\/10.1016\/j.oraloncology.2021.105525","journal-title":"Oral Oncol"},{"issue":"1","key":"10938_CR9","doi-asserted-by":"publisher","first-page":"28303","DOI":"10.1038\/s41598-024-78763-y","volume":"14","author":"LF Schuch","year":"2024","unstructured":"Schuch LF, Campagnol D, Schmidt TR, Michel CHT, Garcez TNA, Velho VR, Wagner VP, Castilho RM, Silveira FM, Bologna-Molina R, Martins MAT, Danilevicz CK, Santos-Silva AR, Vargas PA, Martins MD (2024) Investigating the safety of photobiomodulation in oral carcinogenesis: insights into cell proliferation, invasion, and apoptosis via the 4NQO model. Sci Rep 14(1):28303. https:\/\/doi.org\/10.1038\/s41598-024-78763-y","journal-title":"Sci Rep"},{"issue":"4","key":"10938_CR16","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.tripleo.2005.05.067","volume":"101","author":"A Sioga","year":"2006","unstructured":"Sioga A, Economou L, Kaklamanos EG, Antoniades V, Keramidas G, Manthos A, Antoniades K (2006) Ultrastructural changes of the palatal mucosa following application of 4-nitroquinoline-l-oxide (4NQO) in rats subjected to major salivary gland excision. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101(4):487\u2013498. https:\/\/doi.org\/10.1016\/j.tripleo.2005.05.067","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Endod"},{"issue":"4","key":"10938_CR10","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1158\/1940-6207","volume":"11","author":"S Sur","year":"2018","unstructured":"Sur S, Steele R, Aurora R, Varvares M, Schwetye KE, Ray RB (2018) Bitter melon prevents the development of 4-NQO-induced oral squamous cell carcinoma in an immunocompetent mouse model by modulating immune signaling. Cancer Prev Res (Phila) 11(4):191\u2013202. https:\/\/doi.org\/10.1158\/1940-6207","journal-title":"Cancer Prev Res (Phila)"},{"key":"10938_CR7","unstructured":"Tolosa EMC, Rodrigues CJ, Behmer OA, Neto AGF (2003) Manual of techniques for normal and pathological histology. 2nd edn, Manole, S\u00e3o Paulo, pp 44\u201349, 89\u201392, 125\u2013127"},{"issue":"3","key":"10938_CR21","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1007\/s12105-017-0798-x","volume":"11","author":"AM Udager","year":"2017","unstructured":"Udager AM, Chiosea SI (2017) Salivary duct carcinoma: an update on morphologic mimics and diagnostic use of androgen receptor immunohistochemistry. Head Neck Pathol 11(3):288\u2013294. https:\/\/doi.org\/10.1007\/s12105-017-0798-x","journal-title":"Head Neck Pathol"},{"issue":"5","key":"10938_CR14","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/s1368-8375(03)00011-3","volume":"39","author":"M Vered","year":"2003","unstructured":"Vered M, Daniel N, Hirshberg A, Dayan D (2003) Histomorphologic and morphometric changes in minor salivary glands of the rat tongue during 4-nitroquinoline-1-oxide-induced carcinogenesis. Oral Oncol 39(5):491\u2013496. https:\/\/doi.org\/10.1016\/s1368-8375(03)00011-3","journal-title":"Oral Oncol"}],"container-title":["Journal of Molecular Histology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10735-026-10938-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10735-026-10938-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10735-026-10938-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:19:32Z","timestamp":1792271972000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10735-026-10938-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10938"],"URL":"https:\/\/doi.org\/10.1007\/s10735-026-10938-5","relation":{},"ISSN":["1567-2379","1567-2387"],"issn-type":[{"value":"1567-2379","type":"print"},{"value":"1567-2387","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]},"assertion":[{"value":"3 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"282"}}