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Abnormal expression of bcl-2 and bax in rat tongue mucosa during the development of squamous cell carcinoma induced by 4-nitroquinoline 1-oxide

机译:4-硝基喹啉一氧化物诱导的鳞状细胞癌发展过程中大鼠舌黏膜中bcl-2和bax的异常表达

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摘要

4-Nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis is a useful model for studying oral squamous cell carcinoma. The aim of this study was to investigate the expression of bcl-2 and bax during tongue carcinogenesis induced by 4NQO. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. Although no histological changes were induced in the epithelium after 4 weeks of carcinogen exposure, bcl-2 and bax were over-expressed (P < 0.01) in all layers of the ‘normal’ epithelium. The expression levels were the same in all layers of epithelium for both the antibodies used (bcl-2 or bax). In dysplastic lesions at 12 weeks following carcinogen administration, the levels of bcl-2 and bax expression did not increase when compared to negative control with the immunoreactivity for bcl-2 being restricted to the superficial layer of epithelium. In well-differentiated squamous cell carcinoma induced after 20 weeks of treatment with 4NQO, bcl-2 was expressed in some cells of tumour islands. On the other hand, immunostaining for bax was widely observed at the tumour nests. The labelling index for bcl-2 and bax showed an increase (P < 0.05) after only 4 weeks of 4NQO administration. In conclusion, our results suggest that abnormalities in the apoptosis pathways are associated with the development of persistent clones of mutated-epithelial cells in the oral mucosa. Bcl-2 and bax expression appears to be associated with a risk factor in the progression of oral cancer.
机译:4-硝基喹啉1-氧化物(4NQO)诱导的大鼠舌癌发生是研究口腔鳞状细胞癌的有用模型。这项研究的目的是研究bcl-2和bax在4NQO诱导的舌癌发生过程中的表达。将雄性Wistar大鼠分成三组,每组10只动物,并通过其饮用水用50 ppm 4NQO溶液处理4、12或20周。十只动物用作阴性对照。尽管致癌物暴露4周后上皮细胞没有组织学改变,但是bcl-2和bax在“正常”上皮细胞的所有层中都过表达(P <0.01)。对于使用的两种抗体(bcl-2或bax),上皮所有层的表达水平均相同。在致癌物给药后12周的增生性病变中,与阴性对照相比,bcl-2和bax表达的水平没有增加,而bcl-2的免疫反应性仅限于上皮表层。在用4NQO治疗20周后诱导的分化良好的鳞状细胞癌中,bcl-2在肿瘤岛的某些细胞中表达。另一方面,在肿瘤巢中广泛观察到bax的免疫染色。仅4周的4NQO施用后,bcl-2和bax的标记指数显示增加(P <0.05)。总之,我们的结果表明凋亡途径的异常与口腔粘膜中突变的上皮细胞持续克隆的发展有关。 Bcl-2和bax表达似乎与口腔癌进展的危险因素有关。

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