Minicucci E M, Ribeiro D A, da Silva G N, Pardini M I M C, Montovani J C, Salvadori D M F
Department of Dermatology and Radiotherapy, São Paulo State University, UNESP, SP, Brazil.
Exp Toxicol Pathol. 2011 Jul;63(5):483-9. doi: 10.1016/j.etp.2010.03.009. Epub 2010 Apr 10.
The medium-term tongue carcinogenesis assay is a useful model for studying oral squamous cell carcinomas phase by phase. The aim of the present study was to investigate the expression of p53 by immunohistochemistry and examine the DNA sequence of exons 5, 6, 7, and 8 of Tp53 for mutations during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). A total of 30 male Wistar rats were treated with 4-nitroquinoline 1-oxide in their drinking water for 4, 12, and 20 weeks at a dose of 50 ppm. Ten animals were used as negative controls. No histopathological changes in the tongue epithelia were observed in the control group or in the treatment group after 4 weeks of 4NQO. Following 12 weeks of treatment, hyperplasia as well as epithelial dysplasia was found in both mild and moderate forms. At 20 weeks, moderate and/or severe oral dysplasia and squamous cell carcinoma of the tongue were found, and the majority of animals had squamous cell carcinoma. The levels of p53 protein were increased (p < 0.05) in pre-neoplastic lesions and in squamous cell carcinomas in some of the tumor cells in squamous cell carcinomas. No mutations were found in any of the exons that were evaluated after the 4-, 12-, or 20-week treatments. Taken together, our results suggest that p53 expression may be an important event in the malignant conversion, whereas Tp53 mutations are not involved in the multi-step tongue carcinogenesis of Wistar rats induced by 4NQO.
中期舌癌发生试验是一个逐阶段研究口腔鳞状细胞癌的有用模型。本研究的目的是通过免疫组织化学研究p53的表达，并检测在4-硝基喹啉1-氧化物（4NQO）诱导的大鼠舌癌发生过程中Tp53基因第5、6、7和8外显子的DNA序列是否发生突变。总共30只雄性Wistar大鼠在饮水中以50 ppm的剂量接受4-硝基喹啉1-氧化物处理4周、12周和20周。10只动物用作阴性对照。在4NQO处理4周后，对照组和处理组的舌上皮均未观察到组织病理学变化。处理12周后，发现轻度和中度的增生以及上皮发育异常。在20周时，发现中度和/或重度口腔发育异常以及舌鳞状细胞癌，并且大多数动物患有鳞状细胞癌。在癌前病变和鳞状细胞癌的一些肿瘤细胞中，p53蛋白水平升高（p < 0.05）。在4周、12周或20周处理后评估的任何外显子中均未发现突变。综上所述，我们的结果表明p53表达可能是恶性转化中的一个重要事件，而Tp53突变不参与4NQO诱导的Wistar大鼠舌癌多步骤发生过程。
