PHENOTYPE OF PRENEOPLASTIC AND NEOPLASTIC LIVER-LESIONS DURING SPONTANEOUS LIVER CARCINOGENESIS OF LEC RATS
PHENOTYPE OF PRENEOPLASTIC AND NEOPLASTIC LIVER-LESIONS DURING SPONTANEOUS LIVER CARCINOGENESIS OF LEC RATS
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DOI：
10.1093/carcin/11.10.1857
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发表时间：
1990-10-01
期刊：
影响因子：
4.7
通讯作者：
MORI, M
中科院分区：
文献类型：
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作者：
SAWAKI, M;ENOMOTO, K;MORI, M
我们研究了重度遗传性肝炎恢复后LEC大鼠肿瘤前病变的发生率和表型，并与化学性肝癌肝病变进行了比较。168只大鼠（公鼠90只，母鼠78只）在出生第20周至第122周的不同时间对肝脏进行7种组织化学标记物染色。葡萄糖-6-磷酸酶（G6Pase）、腺苷三磷酸酶（ATPase）和非特异性酯酶（ES）作为阴性标记物。-谷氨酰转移酶（GGT）、胎盘型谷胱甘肽- s转移酶（GSTP）、酯酶同工酶L-1 （L1）和。以-胎蛋白（AFP）为阳性标记物。对LEC大鼠肝脏病变发生率的研究显示，肝灶、结节和肝细胞癌（HCCs）的顺序发展与化学诱导的肝癌相似。这些病变在雄性LEC大鼠中比雌性LEC大鼠出现得更早、更频繁，提示激素环境在自发性HCC发展中的重要性。对LEC大鼠自发性肝病变的组织化学分析表明，GSTP是化学性肝癌发生中最可靠的标志物。自发和化学诱导的肝脏病变中，除L1外，其他标志物的表达没有本质差异，这被认为与异种代谢有关。本研究结果表明，自发肝癌和化学诱导肝癌都可能通过表型相似的肿瘤前过程发展。此外，LEC大鼠在癌变促进阶段表现出独特的慢性肝损伤（肝细胞死亡和再生）。LEC大鼠HCC发展的自然历史与人类HCC相似，后者通常与慢性肝损伤有关。因此，LEC大鼠为研究人类肝癌的发展过程和潜在机制提供了一个有用的模型。
The incidence and phenotype of preneoplastic liver lesions appearing in LEC rats after recovery from severe hereditary hepatitis were studied in comparisons with the liver lesions appearing in chemical liver carcinogenesis. The livers of 168 rats (90 male, 78 female) were stained for seven histochemical markers at different time periods from the 20th week to the 122nd week of life. Glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase) and non-specific esterase (ES) were used as negative markers. Gamma-glutamyltransferase (GGT), glutathione-S-transferase placental form (GSTP), esterase isozyme L-1 (L1) and .alpha.-fetorotein (AFP) were used as positive markers. The study on the incidence of liver lesions in the LEC rats revealed sequential development of liver foci, nodules and hepatocellular carcinomas (HCCs) similar to those seen in chemically induced liver carcinogenesis. These lesions appeared earlier and more frequently in male LEC rats than in female ones, suggesting the importance of hormonal environment in spontaneous HCC development. The histochemical analysis of spontaneous liver lesions in LEC rats showed that GSTP was the most reliable marker as previously reported in chemical liver carcinogenesis. There was no essential difference in the expression of the markers in spontaneous and chemically induced liver lesions except for L1, which is considered to be related to xenobiotic metabolism. The results of this study suggest that both spontaneous and chemically induce liver cancer may develop by passing through phenotypically similar preneoplastic processes. In addition, the LEC rat uniquely showed chronic liver damage (hepatocyte death and regeneration) at the promotion stage of carcinogenesis. Such a natural history of HCC development in LEC rats is similar to that of human HCC which is frequently associated with chronic liver damage. Thus, the LEC rat provides a useful model for studying the process and underlying mechanisms of human liver cancer development.