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

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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.