The application of the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) can initiate and promote the development of oral squamous cell carcinoma of the tongue and buccal mucosa. In this study the level of expression of various markers related to the development of programmed cell death (PCD) in the respective oral carcinomas was analyzed. Sixteen male and female Syrian hamsters (Mesocrietus auratus) were treated with 0.05% DMBA for 16 weeks. Immunohistochemistry was used to observe the expression of p53, proliferating cell nuclear antigen (PCNA), Bcl-2, and nucleosome formation. Single-strand conformational polymorphism (SSCP) for exons 2-9 and sequence analysis of exon 9 of the p53 gene from normal buccal or tongue mucosa as well as the squamous cell carcinomas from the buccal mucosa or the tongue were determined. p53 (wild type) expression was significantly reduced in the tongue dysplastic mucosa or squamous cell carcinoma. The SSCP disclosed banding shifts or new bands in exons 2/3, 4, 8, and 9 for the tongue or buccal oral carcinomas (five of each). In exon 9 the mutation in codon 307 (ala)GCC-GTC(val) was present in the tongue but not in the buccal carcinoma. Other markers included the level of PCNA. PCNA was initially lower in the premalignant tongue lesions but increased in oral squamous cell carcinoma at both sites. In contrast, the amount of nucleosome formation in the tongue carcinomas was less than the level noted for buccal cancers but premalignant dysplasias in the tongue mucosa exhibited higher levels. The inhibitor of PCD, Bcl-2 was lower for dysplasias and carcinomas of the tongue compared to similar lesions of the buccal mucosa. These results indicate that oral carcinomas of different anatomical sites can exhibit differences in growth, oncogene mutation expression, and the development of PCD. The differences in Bcl-2 and nucleosome formation may signify their influence on oncogene expression and growth potential for developing transformed clones and established oral carcinomas.
"Oral squamous cell carcinoma (OSCC) is a deadly malignancy, accounting for more than 90% of malignant tumors of the oral cavity worldwide . Although there has been considerable progress in the understanding of genetic and molecular alterations related to its development , the exact molecular mechanism underlying its formation as well as progression has yet to be established in the literature . "
[Show abstract][Hide abstract] ABSTRACT: Galectin-3 (Gal3) has been implicated in the development of different tumors because of its involvement in the Wnt signaling pathway by promoting beta-catenin translocation into the nucleus. The APC protein, a negative regulator of this pathway, has been strongly implicated in the development of colon cancer, but still has an undetermined role in the formation of oral cancer. Therefore, this study aimed to evaluate the relationship between Gal3, the Wnt signaling pathway, and APC expression in dysplasias and carcinomas developed experimentally in mice. Sixty galectin-3-deficient (Gal3(-/-)) and 60 wild-type (Gal3(+/+)) mice were early employed to be treated with the carcinogen 4NQO for 16 weeks and killed at either week 16 or week 32. Tongues were removed, processed and embedded in paraffin blocks. Sections 5 μm thick were made, and then stained by H&E to establish the diagnosis of dysplasia and carcinoma. Sections of 2 μm thickness were made to detect APC expression in these lesions by immunohistochemistry. Oral carcinogenesis occurred in both groups of mice, but no statistical difference was reached. APC expression was exclusively seen in the cytoplasm of all lesions studied. In the intragroup analysis, the majority of dysplasias and carcinomas exhibiting higher APC immunoreactivity was observed in Gal3(-/-) mice compared to Gal3(+/+) mice, but no significant difference was found. However, a statistical difference was only observed between dysplastic lesions from two mice. Our results showed that neither the absence of Gal3 nor the APC protein appears to play a role in malignant transformation of the tongue.
International journal of clinical and experimental pathology 07/2014; 7(6):3255-63. · 1.89 Impact Factor
"Histopathological changes in the tongue mucosa following the application of DMBA or administration of 4NQO produced from hyperplasia, different grades of dysplasia, and carcinoma in situ to invasive squamous cell carcinoma. These findings are fully in line with previous reports that used these experimental systems (Nishimura, 1999; Schwartz et al., 2000; Okazaki et al., 2002). It is important to stress that in humans the lateral border and ventral surface of the tongue are frequent sites of carcinoma (Ohne et al., 1985). "
[Show abstract][Hide abstract] ABSTRACT: The most used animal models in oral cancer research are the hamster treated by dimethylbenzanthracene (DMBA), and the rat treated by 4-nitroquinoline 1-oxide (4NQO). The purpose of this study was to compare the DMBA-induced hamster tongue carcinogenesis and 4NQO-induced rat tongue carcinogenesis by means of morphological analysis. Male Wistar rats were distributed into three groups of ten animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. A total of 18 Syrian golden hamsters were submitted to 0.5% DMBA (dissolved in acetone) topical application three times/week for 4, 12 and 20 weeks. The primary histopathological change i.e., hyperplasia and hyperkeratosis, was evidenced after 4 weeks treatment with DMBA. Regarding 12 weeks treatment, 4NQO and DMBA were able to induce morphological changes as depicted by hyperplasia and dysplasia. At 20 weeks, squamous cell carcinoma was found in the majority of animals for both carcinogens used. Taken together, our results suggest that the hamster experimental model disclosed aspects related with tongue carcinogenesis in lesser time than rats. Probably, such discrepancies depend strongly on route of administration and the susceptibility with respect to animal species.
Journal of Experimental Animal Science 12/2006; 43(3):219-227. DOI:10.1016/j.jeas.2006.09.001
"In around 35% of the cases, regional disease is already present by the time of the diagnosis, reducing the 5-year survival rate to values lower than 20% (Dias et al., 2001). Some studies conducted in animal models (Von Pressentin et al., 1999 and Schwartz et al., 2000) have tried to verify the effects of chemical carcinogens in various tissues, including oral mucosa , as it seems to have a significant role in the metabolic activation of carcinogens due to the amount of some enzymes responsible for this metabolic process. According to Von Pressentin et al. (1996), the tongue mucosa has a larger amount of these enzymes than other regions of the oral cavity, which raises a possible explanation for the higher aggressiveness and frequency of SCC in this site in particular. "
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