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Toxicologic Pathology
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Greater Expression of Transforming Growth Factor {alpha} and Proliferating Cell Nuclear Antigen Staining in Mouse Hepatoblastomas Than Hepatocellular Carcinomas Induced by a Diethylnitrosamine-Sodium Phenobarbital Regimen

Tetsuya Sakairi

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan, 4307434{at}mitsubishi-pharm.co.jp

Kiyoshi Kobayashi

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Kazuhiro Goto

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Miyoko Okada

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Manami Kusakabe

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Takayuki Tsuchiya

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Jiro Sugimoto

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Fumiko Sano

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Mamoru Mutai

Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 100-5, Yana, Kisarazu, Chiba 292-0812, Japan

Transforming growth factor {alpha} (TGF-{alpha}) is a potent stimulator of normal hepatocyte proliferation, considered to have relationship to the liver regeneration or carcinogenesis. In this study, we investigated immunohistochemically the association between expression of TGF-{alpha} and cell proliferation activity in mouse hepatoblastoma s (HBs) and hepatocellular carcinomas (HCCs) induced in B6C3F1 mice by diethylnitrosamine and sodium phenobarbital. The TGF-{alpha}-positive rate in HBs (29.2%) was significantly higher than that in HCCs (12.7%). Likewise, the proliferating cell nuclear antigen-positive rate (22.2%) was higher than the HCC value (14.5%). On the individual data for both TGF-{alpha} and PCNA, most of the HBs showed higher positive rates than HCCs. In HBs, TGF-{alpha} was localized only in the nuclei, whereas some HCC cells stained positive both in their nuclei and cytoplasm (0.6%). These results suggest expression of TGF-{alpha} and its localization might be linked to cell proliferation and play a role in malignant progression of mouse HBs.

Key Words: B6C3F1 mice • cell proliferation • hepatoblastoma • immunohistochemistry • liver • transforming growth factor {alpha}.

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Toxicologic Pathology, Vol. 29, No. 4, 479-482 (2001)
DOI: 10.1080/01926230152499962


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[Abstract] [Full Text] [PDF]


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