EARLY EVENTS IN CHEMICALLY INDUCED RAT HEPATOCARCINOGENESIS

该项目是为了研究化学过程中的事件顺序而发起的 联合应用鼠肝癌模型诱发肿瘤的实验研究 定量双向凝胶电泳(2D-PAGE)。结果 到目前为止所获得的结果包括：(1)分析多肽之间的差异 正常大鼠肝脏和癌前及癌变结节 Solt-Farber方案(“耐药肝细胞”模型)或VIA 喂饲无遗传毒性的过氧化物体增殖诱导剂环丙贝特， 显示出很少的定性多肽差异，但数量众多； (2)多肽在癌前病变和肿瘤个体中的表达 通过Solt-Farber方案或环丙贝特诱导的结节非常 相似的，暗示有显著的“同质性”而不是“异质性” 多肽在早期皮损中的表达；(3)ALL Solt-Farber 产生的结节对γ-谷氨酰转肽酶都有很强的染色 (GGT)活性与胎盘型谷胱甘肽-S-转移酶 (GST-P)，而在环丙贝特诱导的结节中GGT的表达 S肝脏GST-P水平与对照组差异不显著；(4) 在Solt-Farber诱导过程中发现了四种定性多肽 结节与正常肝脏相比。其中两个是多肽B(PI C(pI为6.75/24 kDa)和C(pI为6.75/24 kDa 环丙贝特诱导和Solt-Farber诱导的癌前病变和肿瘤 结节。此外，还有5种膜相关的(5.25/59 kDa，5/30/33 kDa， 5.25/27 kDa、6.82/23.5 kDa和6.75/21 kDa)和四个胞质 多肽(6.20/45 kDa、5/85/36 kDa、5.06/34 kDa、6.00/24 kDa) 在癌和肿瘤性结节中协同表达 环丙贝特和Solt-Farber肝癌模型。

The project was initiated to study the sequence of events during chemically induced neoplasia using the rodent hepatoma model in combination with quantitative two-dimensional gel electrophoresis (2D-PAGE). Results obtained to date include: (1) analysis of polypeptide differences between normal rat liver and preneoplastic and neoplastic nodules generated using either the Solt-Farber regimen ("resistant hepatocyte" model) or via feeding the nongenotoxic inducer of peroxisome proliferation, ciprofibrate, revealed few qualitative but numerous quantitative polypeptide differences; (2) polypeptide expression in individual preneoplastic and neoplastic nodules induced via the Solt-Farber protocol or with ciprofibrate was very similar, suggesting a marked "homogeneity" rather than "heterogeneity" of polypeptide expression among the early lesions; (3) all Solt-Farber generated nodules stained strongly both for gamma-gutamyltranspeptidase (GGT) activity and for the placental form of glutathione-S-transferase (GST-P), while in the ciprofibrate induced nodules the expression of GGT and s GST-P was not significantly different than control liver levels; (4) four qualitative polypeptide differnces were noted in Solt-Farber-induced nodules as compared to normal liver. Two of these, polypeptides B (pI 6.25/41 kDa) and C (pI 6.75/24 kDa) were expressed in both ciprofibrate-induced and Solt-Farber-generated preneoplastic and neoplastic nodules. In addition five membrane-associated (5.25/59 kDa, 5/30/33 kDa, 5.25/27 kDa, 6.82/23.5 kDa, and 6.75/21 kDa) and four cytosolic polypeptides (6.20/45 kDa, 5/85/36 kDa, 5.06/34 kDa, 6.00/24 kDa) were coordinately expressed in both preneoplassic and neoplastic nodules from both ciprofibrate and Solt-Farber hepatocarcinogenesis models.