title: Cyclooxygenase 2 and Prostaglandin E2 are not Involved in N-Nitrosodiethylamine-Initiated Early Rat Hepatocarcinogenesis.
abstract: The present study was undertaken to investigate the effect of dietary supplementation with nimesulide or eugenol on N-nitrosodiethylamine (DEN)-initiated early hepatocarcinogenesis in F344 male rats. Both compounds did not alter the expression of cytochrome P450 (CYP) 2E1, the enzyme that plays a major role in the activation of DEN to genotoxic products; however, nimesulide induced the expression of CYP1A1. Western blot analysis revealed that COX-1 and COX-2 protein expressions were not modulated by DEN compared with normal controls. Furthermore, post-initiation feeding with nimesulide or eugenol did not modulate COX-2 protein expression in normal or DEN-treated rats, whereas eugenol significantly increased the liver prostaglandin E(2) (PGE(2)) levels of DEN-injected animals compared with the DEN controls. Ultimately, nimesulide or eugenol did not modify DEN-induced hepatocarcinogenesis as evidenced by insignificant changes in the number and size of preneoplastic placental glutathione S-transferase (GST-P) positive liver foci compared with the DEN controls. These results suggest that COX-2, as well as prostaglandin E(2), may play no role in the post-initiation development of DEN-induced rat hepatocarcinogenesis at an early stage.
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Said
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
authors.forename: Pornsiri
authors.initials: P
authors.lastname: Pitchakarn
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Asamoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shirai