Experimental study of oral carcinogenesis by carcinogens possibly endogenously formed in human

实验采用Fischer 344男性比率。用N-亚硝基-2，6-二甲基吗啉(NDMM)10 mg/l或20 mg/l饮水灌胃40周，造成大鼠鼻腔、舌、食道肿瘤。对照组饮水中加入10ppm的4-硝基喹啉-1-氧化物(4-NQO)，连续24周，取舌肿瘤标本。舌部病变按组织学类型分为增生型、异型、乳头状瘤和癌。然后进行环氧合酶-2(COX-2)免疫组织化学染色。在正常舌上皮中，COX-2仅在基底层呈弱阳性表达。但随着病变的进展，染色面积和染色强度逐渐增大，在癌组织中最为明显。用免疫印迹法检测COX-2蛋白的表达。COX-2蛋白表达较正常舌上皮高5.5倍。COX-1蛋白表达未见增加。提示COX-2蛋白的表达与舌癌的发生发展有关。现在，类似的分析也在鼻腔肿瘤中进行。作为未来的工作，我们正在计划使用COX-2特异性抑制剂的实验，以评估化学预防口腔癌的可能性。

Fischer 344 male rate were used for the experiments. Rats were administered 10mg/1 or 20mg/1 of N-nitoso-2,6-dimethylmorpholine (NDMM) in drinking water for 40 weeks and tumors at nasal cavity, tongue and esophgus were obtained. As a control, 10ppm of 4-nitroquiniline 1-oxide (4-NQO) in drinking water was given for 24 weeks and tongue tumors were obtained. Tongue lesions were histologically classified into hyperplasias, dysplasias, papillomas and carcinomas. Then, immunohistochemical staining for cyclooxygenase-2 (COX-2) were performed in these lesions. In healthy tongue epithelium, COX-2 was weakly positive only at basal layer. But, staining area and intensity were increased in parallel with the progression of the lesions and most prominent in carcinomas. Furthermore, the expression of COX-2 protein was analyzed by western blot. The expression of COX-2 protein was increased by 5.5 fold compared with that of healthy tongue epithelium. On the other hand, the expression of COX-1 protein was not increased. From these findings, it is suggested that the expression of COX-2 protein was involved in the development of tongue carcinomas. Now, the similar analysis was ongoing in the tumors of nasal cavity. As future work, we are planning the experiments using specific inhibitor of COX-2 to evaluate the possibility of chemoprevention of oral cancer.