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目的:研究DNA损伤修复关键酶脱嘌呤/脱嘧啶核酸内切酶(apurinic/apyrimidinic endonuclease 1Aep1)在大鼠肝细胞癌形成过程的动态变化,初步探讨Apel与肝细胞癌发生、发展的关系。方法:采用改良法建立二乙基亚硝胺(diethylnitrosamine,DEN)诱发大鼠原发性肝癌模型应用免疫组化SP法检测Ape1和PCNA在不同诱癌阶段的表达情况。结果:正常大鼠肝脏组织中Ape1呈胞核高表达,在不同诱癌阶段的肝脏组织中Ape1表达特征有所改变,呈核浆共同表达或、单纯胞浆表达;随着诱癌时间的延长PCNA表达逐渐增加。结论:在DEN诱导大鼠肝细胞癌模型的过程的同时Ape1具有表达由核内转向浆内的特征,提示核内DNA损伤修复减少导致基因突变增加,可能是肝细胞癌发生、发展的重要机制之一。
OBJECTIVE: To investigate the dynamic changes of apurinic / apyrimidinic endonuclease 1Aep1 in rat hepatocellular carcinoma (HCC), a key factor in DNA damage repair, and to investigate the relationship between Apel and the occurrence and development of hepatocellular carcinoma. Methods: A modified hepatoma model of rat induced by diethylnitrosamine (DEN) was established. Immunohistochemical SP method was used to detect the expression of Ape1 and PCNA at different stages of cancer induction. Results: Ape1 was highly expressed in the liver of normal rats. The expression of Ape1 was changed in liver tissues of different stages of carcinogenesis. The expression of Ape1 was either cytoplasm or cytoplasm. With the extension of the duration of cancer induction PCNA expression gradually increased. CONCLUSION: Ape1 has the characteristic that the expression changes from the nucleus to the nucleus in the process of DEN-induced hepatocellular carcinoma. It suggests that the reduction of DNA damage in nucleus leads to the increase of gene mutation, which may be an important mechanism of the occurrence and development of hepatocellular carcinoma one.