Ribeiro Daniel A, Salvadori Daisy M F, Marques Mariângela E A
Department of Pathology, Center for Genotoxins and Carcinogens Evaluation, TOXICAN, Botucatu Medical School, UNESP, SP, Brazil.
Int J Exp Pathol. 2005 Dec;86(6):375-81. doi: 10.1111/j.0959-9673.2005.00444.x.
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.
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。本研究的目的是调查4NQO诱导舌癌发生过程中bcl-2和bax的表达。将雄性Wistar大鼠分成三组，每组10只，通过饮用水给予50 ppm的4NQO溶液，持续4、12或20周。10只动物作为阴性对照。虽然致癌物暴露4周后上皮未诱导出组织学变化，但“正常”上皮的所有层中bcl-2和bax均过度表达（P < 0.01）。所用的两种抗体（bcl-2或bax）在上皮的所有层中的表达水平相同。致癌物给药12周后的发育异常病变中，与阴性对照相比，bcl-2和bax的表达水平没有增加，bcl-2的免疫反应性仅限于上皮的表层。在用4NQO治疗20周后诱导的高分化鳞状细胞癌中，bcl-2在肿瘤岛的一些细胞中表达。另一方面，在肿瘤巢中广泛观察到bax的免疫染色。仅在给予4NQO 4周后，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异常与口腔黏膜中突变上皮细胞的持续克隆的发展有关。Bcl-2和bax的表达似乎与口腔癌进展中的一个危险因素有关。
