Close Relation of Transforming Growth Factor-α Positive Hepatic Foci to Hepatocellular Tumor Development in the Rat

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概要

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• The question of whether transforming growth factor-α (TGF-α) might be a useful marker of preneoplastic lesions during hepatocarcinogenesis was investigated using a medium-term liver carcinogenesis bioassay (Ito test) extended to 50 weeks. Male F344 rats, 6 weeks of age, received a single i.p. injection of 200 mg/kg diethylnitrosamine (DEN), then after 2 weeks, the animals were divided into four groups. Groups 1 and 2 were maintained on tap water supplemented with 10 ppm of N-nitrosomorpholine (NMOR), a genotoxic carcinogen, for 48 or 6 weeks, respectively. Animals in Group 3 were maintained on basal diet and tap water ad libitum as controls. Group 4 was included as the vehicle control and was maintained until experimental week 50. Two-thirds partial hepatectomy was performed on all rats at the end of week 3 of the experiment. Histopathology and immunohistochemical investigations of glutathione S-transferase placental form (GST-P) and TGF-α of the liver were performed sequentially at experimental weeks 8, 12, 20, 35 and 50. The numbers of TGF-α positive lesions were significantly lower than those of GST-P positive foci at all experimental time points. In contrast, the mean size values of TGF-α positive liver lesions in the continuous and 6-week treatments of DEN/NMOR, and the DEN alone protocol, were larger than those of their GST-P positive counterparts from week 35. Bromodeoxyuridine (BrdU) labeling indices for TGF-α positive foci and hepatocellular adenomas at week 20 were clearly higher than those for TGF-α negative lesions. In conclusion, the overexpression of TGF-α can be immunohistochemically detected in large hepatocellular lesions demonstrating increased levels of DNA synthesis. Therefore TGF-α may be a marker of a relatively late, progression stage of hepatocarcinogenesis.

• 日本毒性病理学会の論文
• 2006-06-01

著者

• HAGIWARA Akihiro

  DIMS Institute of Medical Science, Inc.

• TAMANO Seiko

  DIMS Institute of Medical Science, Inc.

• 高橋 智

  首都大学東京 大学院理工学研究科機械工学専攻

• Sano Masashi

  DIMS Institute of Medical Science, Inc.

• SHIRAI Tomoyuki

  Department of Pathology, Nagoya City University Medical School

• Tamano S

  Dims Institute Of Medical Science Inc.

• Tamano Seiko

  Dims Inst. Medical Sci. Inc.

• Hagiwara A

  Dims Institute Of Medical Science Inc.

• Hagiwara Akihiro

  Dims医科学研究所

• Hagiwara Akihiro

  大阪市立大学 医学部病理学第1

• Hagiwara Akihiro

  Dims Inst. Medical Sci. Inc.

• KAWABE Mayumi

  DIMS Institute of Medical Science, Inc.

• ICHIHARA Toshio

  DIMS Institute of Medical Science, Inc.

• ASAMOTO Makoto

  Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Me

• Shirai T

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

• Shirai Tomoyuki

  ボゾリサーチセンター御殿場研究所

• Kawabe Mayumi

  Dims Inst. Of Medical Sci. Inc.

• Kawabe Mayumi

  名古屋市立大学 医学研究科第一病理学

• Kawabe Mayumi

  Dims Inst. Medical Sci. Inc.

• Kawabe Mayumi

  三省製薬

• Ichihara Toshio

  Dims医科学研究所

• Ichihara Toshio

  Dims Institute Of Medical Science Inc.

• Ichihara Toshio

  Department Of Pathology Osaka City University Medical School

• Ichihara Toshio

  大阪市立大学 病理

• 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

• Kuribayashi Masanori

  名古屋市立大学 医学研究科実験病態病理学分野

• Sugimura T

  Cancer Prevention Basic Research Project National Cancer Center Research Institute

• Shibata Masa-aki

  First Department Of Pathology Nagoya City University Medical School

• Mutai Mamoru

  First Department Of Pathology Nagoya City University Medical School

• Shimokawa T

  National Cancer Center Res. Inst. Tokyo Jpn

• SHIBATA Masa-Aki

  Daiyu-kai Institute of Medical Science

• SHIRAI Tomoyuki

  Nagoya City University Medical School

• Sano M

  Dims Institute Of Medical Science Inc.

• Shirai Tomoyuki

  Graduate School Of Medical Sciences Nagoya City University

• Ichihara Toshio

  Department Of Physics Graduate School Of Science Osaka University

• Ichihara Toshio

  Dims Institute Of Medical Science

• Shibata Michiko

  First Department Of Pathology Nagoya City University Medical School

• Takahashi S

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

• Shirai Tomoyuki

  Department Of Biochemistry Niigata College Of Pharmacy

• Shirai T

  大雄会医科学研究所

• Sano Masaki

  Cancer Research Laboratory Taiho Pharmaceutical Co. Ltd.

• Tamano Seiko

  First Department Of Pathology Nagoya City University Medical School

• Sano Masashi

  Dims Institute Of Medical Science Inc.

• Shibata Masa-aki

  1st Dept.pathol. Nagoya City Univ.med.sch.

• Asamoto Makoto

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

• Sugimura T

  Carcinogenesis Division National Cancer Center Research Institute

• Shirai Tomoyuki

  Pathology Group Yakult Central Inst.

• Shibata Michiko

  Development Strategy Department Yamanouchi Pharmaceutical Co. Ltd.

• Hagihara Atsushi

  Department Of Pathology Osaka City University Medical School

• Shibata Masaaki

  First Department Of Pathology Nagoya City University Medical School

• Hagiwara Akihiro

  First Department Of Pathology Nagoya City University Medical School

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