Cyclooxygenase 2 and Prostaglandin E2 are not Involved in N-Nitrosodiethylamine-Initiated Early Rat Hepatocarcinogenesis

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概要

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• 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 E2 (PGE2) 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 E2, may play no role in the post-initiation development of DEN-induced rat hepatocarcinogenesis at an early stage.

• 日本毒性病理学会の論文
• 2009-12-01

著者

• 高橋 智

  首都大学東京 大学院理工学研究科機械工学専攻

• Tamano S

  Dims Institute Of Medical Science Inc.

• Shirai T

  Experimental Pathology And Tumor Biology Graduate School Of Medical Sciences Nagoya City University

• Ogawa Kumiko

  名古屋市立大学 医学研究科実験病態病理学

• Ogawa K

  Nagoya City Univ. Medical School Nagoya

• Asamoto M

  Department Of Experimental Pathology And Tumor Biology Graduate School Of Medical Sciences Nagoya Ci

• Asamoto M

  Department Of Experimental Pathology And Tumor Biology Nagoya City University Graduate School Of Med

• Asamoto Makoto

  国立がんセンター

• Asamoto Makoto

  住友製薬大阪研究所

• Said Mahmoud

  Department of Biochemistry, Faculty of Science, Ain Shams University

• SHIRAI Tomoyuki

  Nagoya City University Medical School

• Shirai Tomoyuki

  Department Of Biochemistry Niigata College Of Pharmacy

• Shirai T

  大雄会医科学研究所

• Asamoto Makoto

  Department Of Experimental Pathology And Tumor Biology Graduate School Of Medical Sciences Nagoya Ci

• Shirai Tomoyuki

  Pathology Group Yakult Central Inst.

• Shirai Tomoyuki

  Nagoya City Univ. Postgraduate School Of Medical Sci. Nagoya

• Ogawa Kumiko

  Department Of Experimental Pathology And Tumor Biology Nagoya City University Graduate School Of Med

• Takahashi Satoru

  Department Of Anatomy And Embryology Biomolecular And Integrated Medical Sciences Graduate School Of

• Ogawa Kumiko

  Department Of Experimental Pathology And Tumor Biology Graduate School Of Medical Sciences Nagoya Ci

• Pitchakarn Pornsiri

  Department Of Experimental Pathology And Tumor Biology Graduate School Of Medical Sciences Nagoya Ci

• Said Mahmoud

  Department Of Biochemistry Faculty Of Science Ain Shams University

• Tamano Seiko

  Daiyu-kai Institute Of Medical Science

• Pitchakarn Pornsiri

  Department of Biochemistry, Faculty of Medicine, Chiang Mai University

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