title: Survivin and inducible nitric oxide synthase production during 4NQO-induced rat tongue carcinogenesis: a possible relationship.
abstract: This study was undertaken to investigate, by immunohistochemistry, the expression of survivin and inducible nitric oxide synthase during 4NQO-induced rat tongue carcinogenesis. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks. Ten animals were used as negative control. Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, survivin and iNOS were expresssed (p<0.05) in some cells of the 'normal' oral epithelium. In pre-neoplastic lesions at 12 weeks following carcinogen exposure, the levels of survivin and iNOS were increased (p<0.05) when compared to negative control, being the strongest effect observed to iNOS. In well-differentiated squamous cell carcinoma induced after 20 weeks of treatment with 4NQO, survivin and iNOS were expressed in some tumor cells. Lack of immunoreactivity for both markers was observed in the negative control group. Taken together, our results support the belief that expression of survivin and iNOS are early events during malignant transformation and conversion of the oral mucosa.
authors.affiliation: Department of Health Sciences, Federal University of Sao Paulo, UNIFESP, SP, Brazil. daribeiro@unifesp.br
authors.forename: Daniel Araki
authors.initials: DA
authors.lastname: Ribeiro
authors.forename: Darcio
authors.initials: D
authors.lastname: Kitakawa
authors.forename: Maria Aparecida Custodio
authors.initials: MA
authors.lastname: Domingues
authors.forename: Luiz Antonio Guimarães
authors.initials: LA
authors.lastname: Cabral
authors.forename: Mariângela Esther Alencar
authors.initials: ME
authors.lastname: Marques
authors.forename: Daisy Maria Favero
authors.initials: DM
authors.lastname: Salvadori
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D000077022:Survivin; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*
chemical_list: C516989:Birc5 protein, rat; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D015112:4-Nitroquinoline-1-oxide; D052247:Nitric Oxide Synthase Type II