4NQO carcinogenesis: a model of oral squamous cell carcinoma / Carcinogenesis inducida por 4NQO: un modelo de carcinoma oral de células escamosas

The experimental oral carcinogenesis induced by the chemical 4-nitroquinoline 1-oxide (4NQO) is one of the most frequent in the study of squamous cell carcinoma of the oral cavity (CCEC). The clear advantage is that the model is very similar to the physiological process of malignancy. The model has clear benefits by and is suitable for applications in therapeutic research.

La carcinogénesis oral experimental inducida por el químico 4-nitroquinolina 1-óxido (4NQO) es uno de los métodos más frecuentes en el estudio del carcinoma de células escamosas de la cavidad oral (CCECO). La clara ventaja del modelo radica en el gran parecido al proceso fisiológico de la neoplasia maligna. El modelo tiene beneficios claros y es adecuado para las aplicaciones de la investigación terapéutica.

Effect of green propolis on oral epithelial dysplasia in rats / Efeito da própolis verde sobre displasias epiteliais orais em ratos

Studies have demonstrated that flavonoid compounds of green propolis have antitumoral activity. STUDY DESIGN: Experimental study. AIMS: To evaluate the effect of a hydroalcoholic extract of green propolis (EPV) on chemically induced epithelial dysplasias in rat tongues. METHODS AND MATERIALS: DMBA was brushed on the lingual dorsum of rats 3x/week on alternate days - 100 (PROP1), 200 (PROP2) and 300 mg/kg (PROP3) EPV was administered orally for 20 weeks. EPV or DMBA were replaced by their vehicles and applied as positive (TUM1 and TUM2) and negative controls (CTR1 and CTR2), respectively. The lingual epithelium was histologically analyzed and graded according a binary system and the WHO classification; the data were compared using ANOVA (*p<0.05). RESULTS: The EPV yield was 41 percent and the flavonoid yield was 0.95±0.44 percent. According to the Binary System, TUM1, TUM2 and PROP1 were considered high risk lesions, with significantly higher morphological alteration rates compared to the other groups (p<0.05), which were considered low risk lesions. Based on the WHO classification, moderate dysplasia was TUM1 and TUM2, mild dysplasia was PROP1, PROP2 and PROP3, and non-dysplastic epithelium was CTR1 and CTR2. CONCLUSION: EPV seems to play an important protective role against chemically-induced lingual carcinogenesis in rats.

Estudos têm demonstrado que componentes hidrossolúveis da própolis verde, flavonóides, apresentam atividade antitumoral. FORMA DE ESTUDO: Estudo experimental. OBJETIVO: Avaliar o efeito do extrato hidroalcoólico de própolis verde (EPV) sobre displasias epiteliais linguais quimicamente induzidas em ratos. MATERIAIS E MÉTODOS: Neste estudo, foi pincelado DMBA (9,10-dimetil-1,2- benzatraceno) no dorso lingual de ratos 3x/semana, em dias alternados, administrado 100 (PROP1), 200 (PROP2) e 300 mg/kg (PROP3) de EPV (v.o.), durante 20 semanas. A substituição do EPV ou DMBA pelos seus veículos foi usada nos controles positivos (TUM1 e TUM2), negativos (CTR1 e CTR2), respectivamente. O epitélio lingual foi analisado histologicamente, graduado pelo Sistema Binário e classificação OMS, e os dados comparados por análise de variância (ANOVA) (p<0,05). RESULTADOS: O rendimento do EPV foi 41,43 por cento e o teor de flavonóides 0,95±0,44 por cento. Segundo o Sistema Binário, TUM1, TUM2 e PROP1 foram considerados lesões de alto risco, apresentando índices de alterações morfológicas significativamente mais elevados (p<0,05), e os demais de baixo risco. Segundo a classificação OMS, observou-se displasia moderada em TUM e TUM2, leve em PROP1, PROP2 e PROP3, e ausente em CTR1 e CTR2. Conclusão: Sugere-se que o EPV possa desempenhar um papel protetor importante durante a carcinogênese lingual quimicamente induzida em ratos. CONCLUSÃO: Sugere-se que o EPV possa desempenhar um papel protetor importante durante a carcinogênese lingual quimicamente induzida em ratos.

Estudo da expressão de galectina-3 em carcinomas de língua de camundongos / Study of the galectin-3 expression in tongue carcinomas of mice

INTRODUÇÃO: A galectina-3 (Gal-3) é uma lectina de mamíferos ligante de resíduos b-galactosídeos. Numerosos estudos têm mostrado que a Gal-3 apresenta importantes papéis na biologia tumoral, atuando em fenômenos como apoptose, metástase e transformação maligna. No entanto, em carcinomas de cabeça e pescoço, a real significância da sua expressão ainda é pouco compreendida. OBJETIVO: O objetivo deste estudo foi avaliar a expressão de Gal-3 em tumores de língua induzidos experimentalmente em camundongos desafiados com o carcinógeno 4-nitroquinolona-1-óxido (4NQO). MATERIAL E MÉTODOS: Quarenta e dois camundongos C57BL/6, machos, foram desafiados com 4NQO na água de beber por 16 semanas e sacrificados em diferentes períodos depois do tratamento. Após o sacrifício, as línguas foram removidas, processadas, coradas por hematoxilina e eosina (HE) e microscopicamente analisadas quanto à presença de carcinoma. Ensaio imuno-histoquímico para detecção do antígeno Gal-3 e análise descritiva da sua expressão nos tumores induzidos foram realizados. RESULTADOS: Ao final do experimento, foram produzidos 15 tumores. No tecido epitelial não-neoplásico, forte imunorreatividade foi observada apenas na camada parabasal. Nas camadas mais superficiais a intensidade de marcação foi mais fraca, e na camada basal variou de ausente a fraca. Todos os carcinomas bem diferenciados exibiram fraca marcação, exceto nas áreas queratinizantes. No único caso de carcinoma pouco diferenciado, forte imunorreatividade para Gal-3 foi observada. CONCLUSÃO: Nossos resultados descritivos mostram que a transformação maligna é acompanhada de redução da intensidade de expressão da Gal-3 e que o aumento da sua expressão com a perda da diferenciação neoplásica sugere a sua vinculação com agressividade tumoral.

BACKGROUND: Galectin-3 (Gal-3) is a b-galactoside-binding mammalian lectin. Numerous studies have demonstrated that Gal-3 plays an important role in tumor biology, acting in some events such as apoptosis, metastasis and malignant transformation. However, in carcinomas of head and neck, the real significance of Gal-3 expression requires a better understanding. OBJECTIVES: The aim of this paper was to evaluate Gal-3 expression in tongue carcinomas experimentally induced in mice challenged with carcinogen 4-nitroquinoline-1-oxide (4NQO). MATERIAL AND METHOD: Forty-two C57BL/6 male mice were challenged with 4NQO in drinking water for 16 weeks and killed at different periods after induction. In each period, their tongues were removed, routinely processed, stained with hematoxylin and eosin (H&E) and microscopically analyzed as to the presence of carcinoma. Immunohistochemical test for Gal-3 and a descriptive analysis of its expression in induced tumors were performed. RESULTS: By the end of the experiment, 15 tumors had been induced. In the non-neoplastic lingual epithelium, strong and weak immunoreactivity for Gal-3 was noted in parabasal and superficial layers, respectively. In the basal layer, Gal-3 expression varied from absent to weak. All the well-differentiated carcinomas showed weak immunoreactivity for Gal-3, except in keratinized areas. The only case of poorly differentiated squamous cell carcinoma indicated strong immunoreactivity for Gal-3. CONCLUSION: Our results show that malignant transformation is associated with reduced expression of Gal-3, whereas its increased expression in poorly differentiated carcinoma seems to be connected with tumor aggressiveness.

Dietary protocatechuic acid during the progression phase exerts chemopreventive effects on chemically induced rat tongue carcinogenesis.

The modifying effects of dietary administration of protocatechuic acid (PCA) during the progression phase of tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. For tumor progression we developed a new animal model, where rats initiated by 4-week treatment of 20 ppm 4-NQO in drinking water, received four cycles of 20 ppm 4-NQO to induce advanced tongue cancer (one cycle: 2 weeks of 4-NQO followed by 2 weeks of tap water), starting at 14 weeks after the initiation. In this model, metastasis of tongue cancer occurred in lungs. Starting two weeks before the cycle treatment with 4-NQO, animals were fed the 2000 ppm PCA containing diet and continued on this diet until the end of the study. At the termination of the experiment (week 32), the incidences of tongue neoplasms and preneoplastic lesions, polyamine levels in the tongue tissue, and cell proliferation activity estimated by morphometric analysis of silver-stained nucleolar organizer regions protein were compared among the groups. Feeding with PCA containing diet during the progression phase significantly decreased the occurrence of advanced tongue squamous cell carcinoma with metastasis (P<0.05) and preneoplasia (hyperplasia and dysplasia) (P<0.001). In addition, PCA exposure decreased polyamine levels in the tongue tissue (P<0.001) during progression phase. Our results suggest that dietary PCA inhibits progression of 4-NQO-induced oral carcinogenesis, and such inhibition might be related to suppression of cell proliferation by PCA.

Induction of mesenchynal neoplasms by DMBA implantation in deep lingual submucosa of male albino rats

45 male albino rats were used to study the effect of deep submucosal implantation of DMBA on lingual carcinogenesis. The results showed development of different mesenchymal neoplasm [fibroma, fibrosarcoma and leiomyosarcoma]. So, this method of implantation could not be used as an ideal animal model for production of single known neoplasm as had been investigated by many investigators before

Efectos tumorigénicos del condensado de humo de cigarros sobre la mucosa labial de ratones IBFI / Tumorigenic effects of cigarette smoke condensate on the labial mucosa of IBFI mice

Con el objetivo de precisar las alteraciones morfológicas producidas por la aplicación de un condensado de humo de cigarrillos sobre la mucosa labial y su relación con el tiempo de aplicación del carcinógeno, se seleccionaron 120 ratones IBFI entre 4 y 6 semanas de nacido. Los animales recibieron alimento y agua ad libitum y fueron divididos en 4 grupos. Dos grupos fueron tratados con carcinógenos, unos de ellos con el benzo (a) pireno y el otro con un condensado de humo de cigarrillos negros. Un tercer grupo fue tratado con acetona y quedó un grupo no tratado como control. Durante 44 semanas se aplicaron 10 *L de las sustancias empleadas en la mucosa labial de los animales 3 veces a la semana. Todos los animales fueron autopsiados y se realizó disección de labio y lengua. En la semana 44 se presentaron carcinoma epidermoides evidentes tanto en los grupos que recibieron benzo (a) pireno como condensado de humo. Las modificaciones hísticas, más relevantes en diferentes etapas fueron la queratinización superficial, el grosor epitelial y la displasia previas a los estadios neoplásticos