Kobayashi K, Kusakabe M, Okada M, Sakairi T, Goto K, Tsuchiya T, Sugimoto J, Sano F, Mutai M
Pharmacokinetics & Toxicology Laboratory, Yokohama Research Center, Mitsubishi-Tokyo Pharmaceuticals Inc, Yokohama, Japan.
Toxicol Pathol. 2000 Sep-Oct;28(5):664-7. doi: 10.1177/019262330002800505.
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.
用含3'-甲基-4-（二甲基氨基）-偶氮苯的饲料喂养雄性Fischer 344大鼠诱发肝细胞癌（HCC），并将其分为实体型、腺管型（高分化或低分化）和小梁型。对细胞增殖动力学及转化生长因子α（TGF-α）进行免疫组织化学定位研究，结果显示，所有实体型（n = 24）和低分化腺管型（n = 6）HCC的细胞核均呈TGF-α阳性。在28例小梁型HCC中，13例（46%）细胞核呈TGF-α染色阳性，12例（43%）呈细胞质染色阳性，3例（11%）为阴性。高分化腺管型HCC中，20例中有7例（35%）细胞核呈阳性染色，另外7例（35%）抗体结合于细胞质，6例（30%）为阴性。通过溴脱氧尿苷（BrdU）标记评估的生长速率顺序为：实体型（38.22%）、低分化腺管型（26.82%）、小梁型（7.98%）和高分化腺管型（2.57%）。对于细胞核、细胞质或TGF反应阴性的小梁型HCC，其值分别为13.39%（n = 13）、3.61%（n = 12）和2.01%（n = 3）。同样，高分化腺管型HCC相应组的BrdU标记指数分别为4.53%、1.91%和1.29%。结果表明，TGF-α表达可能与大鼠HCC的组织病理学分化及细胞增殖有关。
