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Immunohistochemical Localization of Transforming Growth Factor Alpha in Chemically Induced Rat Hepatocellular Carcinomas with Reference to Differentiation and Proliferation
Kiyoshi Kobayashi
Pharmacokinetics & Toxicology Laboratory, Yokohama Research Center, Mitsubishi-Tokyo Pharmaceuticals Inc, Kamoshida-cho, Aoba-ku, Yokohama 227-8502 Japan
Manami Kusakabe
Pharmacokinetics & Toxicology Laboratory, Yokohama Research Center, Mitsubishi-Tokyo Pharmaceuticals Inc, Kamoshida-cho, Aoba-ku, Yokohama 227-8502 Japan
Miyoko Okada
Pharmacokinetics & Toxicology Laboratory, Yokohama Research Center, Mitsubishi-Tokyo Pharmaceuticals Inc, Kamoshida-cho, Aoba-ku, Yokohama 227-8502 Japan
Tetsuya Sakairi
Pharmacokinetics & Toxicology Laboratory, Yokohama Research Center, Mitsubishi-Tokyo Pharmaceuticals Inc, Kamoshida-cho, Aoba-ku, Yokohama 227-8502 Japan
Kazuhiro Goto
Pharmacokinetics & Toxicology Laboratory, Yokohama Research Center, Mitsubishi-Tokyo Pharmaceuticals Inc, Kamoshida-cho, Aoba-ku, Yokohama 227-8502 Japan
Takayuki Tsuchiya
Pharmacokinetics & Toxicology Laboratory, Yokohama Research Center, Mitsubishi-Tokyo Pharmaceuticals Inc, Kamoshida-cho, Aoba-ku, Yokohama 227-8502 Japan
Jiro Sugimoto
Pharmacokinetics & Toxicology Laboratory, Yokohama Research Center, Mitsubishi-Tokyo Pharmaceuticals Inc, Kamoshida-cho, Aoba-ku, Yokohama 227-8502 Japan
Fumiko Sano
Pharmacokinetics & Toxicology Laboratory, Yokohama Research Center, Mitsubishi-Tokyo Pharmaceuticals Inc, Kamoshida-cho, Aoba-ku, Yokohama 227-8502 Japan
Mamoru Mutai
Pharmacokinetics & Toxicology Laboratory, Yokohama Research Center, Mitsubishi-Tokyo Pharmaceuticals Inc, Kamoshida-cho, Aoba-ku, Yokohama 227-8502 Japan
Hepatocellular carcinomas (HCCs) were induced in male Fischer 344 rats with dietary 3'-methyl-4-(dimethylamino)-azobenzene treatment and were classified into solid, glandular (well- or poorly differentiated), and trabecular types. Investigation of cell proliferation kinetics and immunohistochemical localization of transforming growth factor alpha (TGF-alpha) demonstrated all solid (n = 24) and poorly differentiated glandular type (n = 6) HCCs to have TGF-alpha-positive nuclei. Nuclear staining of TGF-alpha was also observed in 13 of 28 (46%) trabecular-type HCCs, whereas 12 (43%) exhibited cytoplasmic staining, and 3 (11%) were negative. As for well-differentiated glandular HCCs, 7 of 20 (35%) were positively stained in their nucleus, another 7 (35%) demonstrated antibody binding in the cytoplasm, and 6 (30%) were negative. The order for growth rate evaluated by bromodeoxyuridine (BrdU) labeling was solid (38.22%), poorly differentiated glandular (26.82%), trabecular (7.98%), and well-differentiated glandular (2.57%) types. For trabecular HCCs with nuclear, cytoplasmic, or negative TGF reactions, values were 13.39% (n = 13), 3.61% (n = 12), and 2.01% (n = 3), respectively. Likewise, BrdU-labeling indices for the counterpart groups of well-differentiated glandular type HCCs were 4.53, 1.91, and 1.29%, respectively. The results indicate that TGF-alpha expression might be linked to histopathological differentiation and cell proliferation in rat HCCs.
Key Words: Cell proliferation • differentiation • hepatocarcinogenesis • immunohistory • rat • transforming growth factor-alpha
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Toxicologic Pathology, Vol. 28, No. 5,
664-667 (2000)
DOI: 10.1177/019262330002800505
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