AIM:To study the effect of celecoxib(CXB) on diethylnitrosamine activation through the regulation of cytochrome P450 in a hepatocarcinogenesis model.METHODS:Six-week-old male Sprague-Dawley rats were randomly divided into fi ve groups,a non-treated group(NT) ,a diethylnitrosamine-treated group(DEN) ,a DEN+CXB-treated group(DEN+CXB) ,and CXB 8 d-treated and CXB 32 d-treated groups.The effects of celecoxib on the enzymatic activities of CYP1A1,2A,2B1/2,and 2E1 were assessed in hepatic microsomes 24 h after DEN administration.Changes in CYP1A1 and CYP2B1/2 protein expression were also evaluated.The rate of DEN metabolism was measured by the production of the deethylation metabolite acetaldehyde,and the denitrosation metabolite nitrite.RESULTS:DEN+CXB administration produced a significant increase in the enzymatic activities of CYP2B1/2 and 1A1,whereas it did not change the activities of CYP2A and 2E1,compared to that of the DEN group.CXB treatment for eight days did not produce a signif icant effect on enzymatic activity when compared to the NT group;however,when it was administered for prolonged times(CXB 32 d group) ,the enzymatic activities were increased in a similar pattern to those in the DEN+CXB group.The observed increase in the enzymatic activities in the DEN+CXB group was accompanied by an increase in the CYP2B1/2 protein levels;no changes were observed in the levels of CYP1A1.In vitro,CXB increased the denitrosation of DEN,a pathway of metabolic detoxification.The addition of SKF-525A,a preferential inhibitor of CYP2B,abrogated the denitrosation of DEN.CONCLUSION:These results suggest that the mechanism of action of CXB involves enhancement of the detoxif ication of DEN by an increasing denitrosation via CYP2B1/2. AIM: To study the effect of celecoxib (CXB) on diethylnitrosamine activation through the regulation of cytochrome P450 in a hepatocarcinogenesis model. METHODS: Six-week-old male Sprague-Dawley rats were randomly divided into fi ve groups, a non-treated group (NT), a diethylnitrosamine-treated group (DEN), a DEN + CXB-treated group (DEN + CXB), and CXB 8 d- treated and CXB 32 d-treated groups.The effects of celecoxib on the enzymatic activities of CYP1A1 , 2A, 2B1 / 2, and 2E1 were assessed in the production of the hepatic microsomes 24 h after DEN administration. Changes in CYP1A1 and CYP2B1 / 2 protein expression were also evaluated by the production of the deethylation metabolite acetaldehyde, and the denitrosation metabolite nitrite.RESULTS: DEN + CXB administration produced a significant increase in the enzymatic activities of CYP2B1 / 2 and 1A1, it it did not change the activities of CYP2A and 2E1, compared to that of the DEN group. CXB treatment for eight days did not produce a signif i cant effect on enzymatic activity when compared to the NT group; however, when it was administered for prolonged times (CXB 32 d group), the enzymatic activities were increased in a similar pattern to those in the DEN + CXB group. The observation increase in the enzymatic activities in the DEN + CXB group were accompanied by an increase in the CYP2B1 / 2 protein levels; no changes were observed in the levels of CYP1A1. In vitro, CXB increased the denitration of DEN, a pathway of metabolic detoxification. of SKF-525A, a preferential inhibitor of CYP2B, abrogated the denitrosation of DEN. CONCLUSION: These results suggest that the mechanism of action of CXB involvement enhancement of the detoxification of DEN by an increasing denitation via CYP2B1 / 2.