{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:49:38Z","timestamp":1790027378287,"version":"4.0.1"},"reference-count":20,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,6,14]],"date-time":"2014-06-14T00:00:00Z","timestamp":1402704000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Fapesp","doi-asserted-by":"crossref","award":["2011\/07437-0"],"award-info":[{"award-number":["2011\/07437-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CNPQ","award":["870031\/2005-8"],"award-info":[{"award-number":["870031\/2005-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Most studies have demonstrated 4\u2010<jats:styled-content style=\"fixed-case\">NQO<\/jats:styled-content> toxicity to oral epithelium during oral carcinogenesis induction, but systemic toxicity has been poorly addressed. The aim of this study was to describe the systemic effect of 4\u2010<jats:styled-content style=\"fixed-case\">NQO<\/jats:styled-content> topical application during early phases of oral cancer induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 4\u2010<jats:styled-content style=\"fixed-case\">NQO<\/jats:styled-content> propylene glycol ointment was topically applied on the rat tongue three times a week for 16\u00a0weeks. Local and systemic 4\u2010<jats:styled-content style=\"fixed-case\">NQO<\/jats:styled-content> toxicity was evaluated by body weight gain, hematology, and serum chemistry analyses, histopathology, and proliferating cell nuclear antigen (<jats:styled-content style=\"fixed-case\">PCNA<\/jats:styled-content>) immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant reduction in body weight gain and in white blood cell count as well as significant increase in serum <jats:styled-content style=\"fixed-case\">ALT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">AST<\/jats:styled-content> was observed after 16\u00a0weeks of 4\u2010<jats:styled-content style=\"fixed-case\">NQO<\/jats:styled-content> topical application. Focal hepatic lobular necrosis, renal tubular degeneration, and decreased cellularity in the splenic white pulp were also detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>4\u2010<jats:styled-content style=\"fixed-case\">NQO<\/jats:styled-content> topical application on the tongue of rats for 16\u00a0weeks seems to have caused hepatic, renal, and splenic toxicity. Potential systemic toxicity should be considered to monitor for variables that could interfere in topical oral carcinogenesis experiments.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12190","type":"journal-article","created":{"date-parts":[[2014,6,16]],"date-time":"2014-06-16T18:24:10Z","timestamp":1402943050000},"page":"770-777","source":"Crossref","is-referenced-by-count":15,"title":["Systemic toxic effects during early phases of topical 4\u2010<scp>NQO<\/scp>\u2010induced oral carcinogenesis in rats"],"prefix":"10.1111","volume":"43","author":[{"given":"Ana Rita Ribeiro","family":"Barcessat","sequence":"first","affiliation":[{"name":"General Pathology Department School of Dentistry University of S\u00e3oPaulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Huang","sequence":"additional","affiliation":[{"name":"General Pathology Department School of Dentistry University of S\u00e3oPaulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9511-5078","authenticated-orcid":false,"given":"Gustavo Davi","family":"Rabelo","sequence":"additional","affiliation":[{"name":"Oral Pathology Department School of Dentistry University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via Cristina Perillo","family":"Rosin","sequence":"additional","affiliation":[{"name":"General Pathology Department School of Dentistry University of S\u00e3oPaulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana Gon\u00e7alves Valente","family":"Ferreira","sequence":"additional","affiliation":[{"name":"General Pathology Department School of Dentistry University of S\u00e3oPaulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Gualberto","family":"de Cerqueira Luz","sequence":"additional","affiliation":[{"name":"Oral Surgery Department School of Dentistry University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Corr\u00eaa","sequence":"additional","affiliation":[{"name":"General Pathology Department School of Dentistry University of S\u00e3oPaulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,6,14]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.10004"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2005.07.014"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21694"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2005.10.013"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1981.tb01264.x"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1940-6207.CAPR-09-0058"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.2880160506"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0901-5027(05)80857-4"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-0999-3"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.20531"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0030-4220(84)90312-8"},{"key":"e_1_2_5_13_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1055\/s-0039-1698331","article-title":"Gingival changes in Wistar rats after oral treatment with 4\u2010nitroquinoline 1\u2010oxide","volume":"1","author":"Ribeiro DA","year":"2007","journal-title":"Eur J Dent"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/28.1.56"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0964-1955(95)00086-0"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.4137\/BMI.S10009"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2012.108"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfq144"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfr112"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-010-0109-z"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2003.08.008"}],"container-title":["Journal of Oral Pathology &amp; 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