Studies on the involvement of inflammatory stimuli and immortalization of cells in tongue carcinogenesis and cancer chemoprevention

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Our previous study indicated that expression of COX-2 protein involves in 4-NQO-induced rat tongue carcinogenesis. In this year, therefore, we investigated possible modifying effect of nimesulide, which specific inhibitor of COX-2, on 4-NQO-induced rat tongue tumorigenesis.A total of 97 male F344 rats aged 4 weeks were used. Rats were given 4-NQO (20 ppm in drinking water) for 8 weeks to induced tongue squamous cell carcinoma. They were also fed the diets mixed w* nimesulide at a dose of 0.01% or 0.04% during the initiation (10 weeks) or promotion phase (22 weeks). The experiment was terminated 32 weeks after the start. At the end of the study, the incide* of tongue squamous cell carcinoma were 48% (13/27 rats) in the 4-NQO alone group, 20% (3/15 rats) in 4-NQO+0.01% nimesulide group, 13% (2/15 rats) in the 4-NQO+0.04% nimesulide group, 42% (5/12 rats) in the 4-NQO→0.01% nimesulide group, and 8% (1/12 rats) in the 4-NQO→0.04% nimesulide group. Thus, feeding of nemesulide during either the initiation or promotion pahse *tumorirgenesis significantly inhibited the development of tongue carcinoma (P<0.05). No tongue tum* were present in rats of nimesulide alone (0.04%) and untreated control. These results suggest that a COX-2 sepcific inhibitor nimesulide is applicable for human clinical trial for chemoprevention of tongue cancer. The studies on mechanisms of inhibition are ongoing in our laboratory.It is well known that the treatment of 4-NQO in drinking water specifically prodeces tongue neoplas* However, in the present study, 4-NQO exposure induced squamous cell carcinoma in the palate and gi*of the maxilla as well as tongue carcinoma. Feeding of nimesulide also inhibited the development of th*tumors.