Caracterização histológicas das alterações induzidas por 4-NQO na língua de camundongos: uma análise das alterações epiteliais, morfotoxidade dos orgãos e hematológica

Abstract

Squamous cell carcinoma is a most common malignant lesion in the oral cavity and mainly affects advanced age. In this sense, animal research has helped in understanding the pathogenesis of this disease, as well as in new therapeutic alternatives. Thus, we aimed to evaluate as epithelial alterations of lesions induced in the oral mucosa of mice by 4-nitroquinoline1-oxide (4-NQO). The animals were divided into 4 test groups, being applied in the typical application of 0.5% 4-NQO dissolved in 5 mg / ml propyleneglycol, and a control group which was subjected only to the vehicle 3 times a week during the 4th, 12th, 16th, and 20th weeks. Prior to application, animals are dosed with butylbromide scopolamine to decrease salivary flow. Euthanasia occurred at the 4th, 12th, 16th, and 20th weeks in the test group, while the euthanasia control group occurred only at the 20th week. After euthanasia, sore throat and vomiting of the tongue, esophagus, stomach, spleen and liver were surgically removed and histologically reported. In the microscopic analysis of the tongue, the control group and the 4 weeks did not show changes and architectures of the epithelium, being observed from the 12th week in the presence of basal layer polarity loss and increased nucleus / cytoplasm ratio (p <0.001) with the onset of mild dislocation. In the 16-week group, she presented evolution of epithelial alterations composed by anisonucleosis, anisocytosis, cellular and nuclear pleomorphism (p <0.005) with the presence of moderate to severe displacement. In the 20-week group, carcinomas were found in situ in half of the sample (p <0.001). An immunohistochemistry for ki-67 showed that after 12 (0.75 ± 0.11), 16 (0.75 ± 0.14) and 20 (0.80 ± 0.08) weeks of 4 years in which immunoexpression It was used higher without group control (p = 0.003). Regarding immunostaining for p63, affect a statistically significant difference from the 20th week to the control group (basal layer: p = 0.039; spiny layer: p = 0.032; granular layer: p = 0.021). As for liver toxicity, it was not changed until the 12th. week, but from the 16th week, shows the presence of inflammatory cells. After a 20th week, the results indicate inflammatory cells in the region's ankle, with an animal that develops ballooning cells and hepatocyte necrosis. In the esophagus, the animals develop degrees of dislocation from the 16th week, with the presence of keratin pearls and mitosis. In the stomach toxicity analysis, the presence of inflammatory cells and ectatic vessels was noted from the 16th week, with only two cases of hyperkeratinization. As alterations in the spleen, such as lipofuscin and hemosiderophages, are present in the 20th week, and the other groups are consistent with the normality pattern. A renal analysis showed the appearance of glomerular hemorrhage, hyaline cylinder and vacuolar degeneration of the tubular epithelium from the 12th week. In sum, the findings concluded that the typical application of 4-NQO allowed the development of local carcinoma on the tongue associated with mild esophageal toxicity.