Análise Morfológica da Mucosa Oral de Ratos Submetida à Carcinogênese Experimental pelo Óxido de Nitroquinolina (4NQO)

Abstract

Ratos wistar; Carcinoma in situ; Carcinoma de células escamosas. Wistar rats; Carcinoma in situ; Squamous cell carcinoma. Objecti ve: To induce carcinogenesis on the lingual mucosa of Wistar rats by the administrati on of nitroquinoline oxide (4NQO), relati ng the clinical and microscopic alterati ons developed during the ti me of exposure to the carcinogenic agent. Methods: Twenty rats were allocated to either an experimental (15 animals) or a control (5 animals) group. In the experimental group, the animals were divided into 3 subgroups in which 5 animals received 4NQO during 2 months (A1), 5 during 3 months (A2), and 5 during 4 months (A3), making it possible to detect the diff erent phases of carcinogenesis. Data were presented as descripti ve stati sti cs using the Kruskal-Wallis and Mann-Whitney tests in the SPSS (Stati sti cal Package for the Social Sciences) soft ware, version 13.0. The signifi cance level was set at 5.0%. Results: Both the animal model and the carcinogenic agent used in the study were sati sfactory for inducing similar oral carcinogenesis to the one occurring in humans. The clinical alterati ons were more accentuated in the animals that received the topical applicati ons of 4NQO during 4 months, ranging from leukoplakia to erythroleukoplakias regions. The histopathological alterati ons observed in the oral epithelium were compati ble with the diagnosis of mild, moderate and severe epithelial dysplasia, in situ carcinoma or invasive carcinoma. Conclusion: The severity of the lesions had a direct relati onship with the exposure ti me to 4NQO.

Overexpression of Bcl‐2, SOCS 1, 3 and Cdh 1, 2 are associated with the early neoplasic changes in modified 4‐nitroquinoline 1‐oxide‐induced murine oral cancer model

“…Our findings also confirm that the tongue region to be analyzed is essential in this experimental model, as the histopathological changes were observed exclusively in the mid-and posterior portions of the tongue (5). The results of the descriptive histopathological assessment of the mid-and posterior regions of the tongue confirm the findings of previous studies showing the presence of atypical cells and epithelial dysplasia after 8 weeks of exposure to 4-NQO.…”

“…4‐Nitroquinoline oxide is a carcinogen routinely used to study oral carcinogenesis in rodents. Most commonly, 4‐NQO is used by topical application or administered systemically in the drinking water . The route of administration and dosage of 4‐NQO employed in this study were based on previous studies, which were shown to be well tolerated and pharmacologically active in inducing oral cancer in rats .…”

“…However, it must be noted that we did not assess liver or kidney function and/or histopathological changes of these organs. Most studies using the 4‐NQO model of chemically induced cancer focus on the development and assessment of well‐established tumors , and relatively few studies assess early changes in the oncogenic process. In this study, epithelial dysplasia was clearly established within 8 weeks of exposure to 4‐NQO and interestingly.…”

“…Study models that allow the evaluation of the whole spectrum of oncogenic changes associated with the development of invasive oral cancer are of great value. Experimental models of oral carcinogenesis are routinely used in various laboratory animals . The nitroquinoline oxide (4‐NQO) is a potent inducer of intracellular oxidative stress that may generate changes in DNA.…”