ABSTRACT
Objective To study the expression of vimentin in the tongue mucosa carcinogenesis and to explore its significance in the invasion and metastasis of tongue squamous cell carcinoma .Methods The occurrence of tongue squamous cell carcinoma in rat was induced by means of 4NQO water solution ,and 56 cases in total were collected in the cancerous process ,including normal tongue mucosa ,epithelial hyperplasia ,mild dysplasia ,moderate dysplasia ,severe dysplasia and the tongue tissue specimen of squa‐mous cell carcinoma .The immunohistochemistry was used to evaluate protein expression and real‐time fluorescent quantitative PCR method was used to obtain the expression quantity of mRNA .Results In immunohistochemistry ,with the increase of degree of rat tongue mucosa dysplasia ,the positive rate of vimentin expression increases obviously .The difference between groups was statistical‐ly significant (χ2 =10 .685 ,P<0 .05) .Lesion groups compared with normal group ,their mRNA expression differences all hold sta‐tistical significance(P<0 .05);Mild dysplasia ,moderate dysplasia ,severe dysplasia and squamous cell carcinoma groups were com‐pared with epithelial hyperplasia group .The difference between squamous cell carcinoma group and epithelial hyperplasia group was statistically significant (P<0 .05) .mRNA expression of epithelial hyperplasia ,mild dysplasia ,moderate dysplasia and severe dys‐plasia were respectively 1 .22 times ,1 .28 times ,1 .29 times and 1 .42 times of that of the normal group .Conclusion During rat tongue carcinogenesis induced by 4NQO ,the expression of vimentin was increased with the increase of the degree of pathological change ,which is closely related to the invasion of tumor and could be regarded as a predictor of tongue squamous cell carcinoma .
ABSTRACT
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.
Subject(s)
Animals , Rats , Carcinoma, Squamous Cell/etiology , Tongue Neoplasms/chemically induced , Tongue Neoplasms/ultrastructure , Tongue Neoplasms/veterinary , Neoplasms/chemically induced , Neoplasms/ultrastructure , Mouth Neoplasms/chemically induced , Mouth Neoplasms/ultrastructure , Mouth Neoplasms/veterinary , Rats/anatomy & histology , Rats/injuriesABSTRACT
INTRODUÇÃO: A galectina-3 (GAL3) apresenta importantes papéis na biologia tumoral e recentemente foi mostrada a sua participação na via de sinalização Wnt, translocando a beta-catenina para o núcleo. Expressão alterada de GAL3 e beta-catenina tem sido descrita em cânceres, mas não há estudos avaliando a expressão de ambas em displasias e carcinomas desenvolvidos em modelos de carcinogênese de língua. OBJETIVOS: Estudar a expressão de GAL3 e beta-catenina em lesões displásicas e carcinomas induzidos experimentalmente em língua de camundongos. MATERIAL E MÉTODOS: Vinte camundongos C57BL/6 machos foram desafiados com 4NQO na água de beber por 16 semanas e sacrificados na semana 16 e 32. Após o sacrifício, as línguas foram removidas, processadas, coradas por hematoxilina e eosina (HE) para detecção de displasias e carcinomas. Ensaio imuno-histoquímico foi realizado para determinar o índice de positividade para GAL3 e beta-catenina nessas lesões, bem como uma correlação entre elas em carcinomas. RESULTADOS: O número de camundongos afetados por carcinoma aumentou entre as semanas 16 e 32 (22,2 por cento vs. 88,9 por cento) e o de displasia diminuiu (66,7 por cento vs. 11,1 por cento). Um aumento de células positivas para beta-catenina não membranosa e GAL3 citoplasmática foi observado nas displasias e nos carcinomas, mas essa diferença não foi estatisticamente significativa. No entanto, um aumento estatisticamente significativo de GAL3 nuclear foi observado na evolução de displasia para carcinoma (p = 0,04). Nenhuma correlação foi encontrada entre beta-catenina e GAL3. CONCLUSÃO: Tanto nas displasias quanto nos carcinomas a via de sinalização Wnt está ativa, e o aumento de GAL3 nuclear nos carcinomas sugere um papel na transformação maligna do epitélio lingual.
INTRODUCTION: Galectin-3 plays pivotal role in tumor biology and its participation in Wnt signaling pathway translocating beta-catenin into the nucleus has been recently demonstrated. Altered galectin-3 and beta-catenin expressions have been described in different tumors, however, there are no studies evaluating their expression in dysplasias and carcinomas induced in carcinogenic tongue models. OBJECTIVES: To study galectin-3 and beta-catenin expressions in dysplasias and carcinomas experimentally induced in mouse tongue. METHODS: Twenty C57Bl/6 male mice were treated with 4NQO in their drinking water for 16 weeks and sacrificed at weeks 16 and 32. Tongues were removed, routinely processed, and stained with hematoxylin and eosin to detect dysplasias and carcinomas. An immunohistochemical assay was performed to determine the level of positivity for galectin-3 and beta-catenin in these lesions as well as their correlation in carcinomas. RESULTS: The number of mice affected by carcinomas increased from week 16 to week 32 (22.2 percent vs. 88.9 percent) and the number affected by dysplasias decreased (66.7 percent vs. 11.1 percent). There was an increase in non-membranous beta-catenin- and cytoplasmic galectin-3-positive cells in dysplasias and carcinomas, although this difference was not statiscally significant. Nonetheless, there was a significant increase of nuclear galectin-3-positive cells in the evolution from dysplasia to carcinoma (p = 0.04). There was no correlation between beta-catenin and galectin-3. CONCLUSION: Wnt signaling pathway is active in both dysplasias and carcinomas and the increase of nuclear galectin-3-positive cells in carcinomas suggests its influence on malignant transformation in the tongue epithelium.
Subject(s)
Animals , Mice , Gene Expression , /genetics , Immunohistochemistry , Tongue , beta Catenin/genetics , Mouth NeoplasmsABSTRACT
Spearmint leaves (Mentha spicata L.) contain high levels of antioxidants that are known to protect against both exogenous and endogenous DNA damage. In this study, the protective effects of the hexane fraction (HF), chloroform fraction (CF) and ethyl acetate fraction (EAF) in an ethanol extract from M. spicata were evaluated against 4-nitroquinoline-1-oxide (4-NQO) induced chromosome damage and apoptosis in bone marrow cells of Swiss albino mice. Two (EAF; 80 and 160 mg/ kg body weight - bw) or three (HF and CF; 80, 160 and 320 mg/ kg bw) doses of solvent fractions or vehicle control (25 percent DMSO in water) were administered orally for five consecutive days. Upon the sixth day, 4-NQO was injected intraperitoneally. The animals were killed the following day. Other control groups were comprised of animals treated with either the vehicle control or the various doses of solvent fractions, but with no 4-NQO treatment. 4-NQO induced micro-nucleated polychromatic erythrocytes (MnPCEs) in all the test groups. However, pre-treatment of animals with the solvent fractions significantly reduced the 4-NQO-induced MnPCEs as well as the percentage of apoptotic cells. The reduction of both MnPCE and apoptosis was more evident following the pre-treatment of animals with 160 mg/kg bw EAF.
ABSTRACT
Cashew apple juice (CAJ), produced from the native Brazilian cashew tree (Anacardium occidentale), and has been reported to have antibacterial, antifungal, antitumor, antioxidant and antimutagenic properties. Both the fresh unprocessed juice and the processed juice (cajuína in Portuguese) has been shown to consist of a complex mixture containing high concentrations of anacardic and ascorbic acids plus several carotenoids, phenolic compounds and metals. We assessed both types of juice for their antimutagenic properties against the direct mutagens methyl methanesulfonate (MMS) and 4-nitroquinoline-N-oxide (4-NQO) and the indirect mutagen benzo[a]pyrene (BaP) using pre-treatment, co-treatment and post-treatment assays with Salmonella typhimurium strains TA100, TA102, and TA97a. In pre-treatment experiments with strains TA100 and TA102 the fresh juice showed high antimutagenic activity against MMS but, conversely, co-treatment with both juices enhanced MMS mutagenicity and there was an indication of toxicity in the post-treatment regime. In pre-, co-, and post-treatments with TA97a as test strain, antimutagenic effects were also observed against 4-NQO and BaP. These results suggest that both fresh and processed CAJ can protect the cells against mutagenesis induced by direct and indirect mutagens.
ABSTRACT
Objective To validate feasibility of comet assay as a tool for detecting DNA damage induced by various types of chemical mutagens.Study of DNA damage induced by4chemicals on human lymphocytes was carried out in vitro.Methods Human lymphocytes were exposed to4-nitroquinoline-1-oxide(4NQO,a UV-mimetic agent ),methyl methanesulfonate(MMS,an alkylating agent ),Bleomycin(BLM,a radiamimetic agent )and Mitomycin(MMC,a DNA crosslink agent )for3h,the DNA single strand breaks(SSB)induced by4chemicals were measured immediately(0h-incubation)and21h-incubation after3h-exposure to the chemicals with comet assay.Results It was found that the SSB induced by4NQO,MMS and BLM,which revealed a dose-response relationship(P