Sawaki M, Enomoto K, Takahashi H, Nakajima Y, Mori M
Department of Pathology, Sapporo Medical College, Japan.
Carcinogenesis. 1990 Oct;11(10):1857-61. doi: 10.1093/carcin/11.10.1857.
The incidence and phenotype of preneoplastic and neoplastic liver lesions appearing in LEC rats after recovery from severe hereditary hepatitis were studied in comparison 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-fetoprotein (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 positive 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 induced 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.
研究了严重遗传性肝炎恢复后的LEC大鼠出现的癌前和肿瘤性肝损伤的发生率及表型，并与化学性肝癌发生中出现的肝损伤进行比较。在168只大鼠（90只雄性，78只雌性）生命的第20周 至第122周的不同时间段，对其肝脏进行7种组织化学标志物染色。葡萄糖-6-磷酸酶（G6Pase）、三磷酸腺苷酶（ATPase）和非特异性酯酶（ES）用作阴性标志物。γ-谷氨酰转移酶（GGT）、谷胱甘肽S-转移酶胎盘型（GSTP）、酯酶同工酶L-1（L1）和甲胎蛋白（AFP）用作阳性标志物。对LEC大鼠肝损伤发生率的研究显示，肝灶、结节和肝细胞癌（HCC）呈序贯性发展，类似于化学诱导的肝癌发生中所见。这些病变在雄性LEC大鼠中出现得更早且更频繁，提示激素环境在自发性HCC发生中的重要性。对LEC大鼠自发性肝损伤的组织化学分析表明，GSTP是最可靠的阳性标志物，正如先前在化学性肝癌发生中所报道的那样。除了被认为与异生物质代谢有关的L1外，自发性和化学诱导性肝损伤中标志物的表达没有本质差异。本研究结果表明，自发性和化学诱导性肝癌可能都通过表型相似的癌前过程发展而来。此外，LEC大鼠在致癌作用的促进阶段独特地表现出慢性肝损伤（肝细胞死亡和再生）。LEC大鼠中HCC发生的这种自然史与经常伴有慢性肝损伤的人类HCC相似。因此，LEC大鼠为研究人类肝癌发生的过程及潜在机制提供了一个有用的模型。
