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目的：观察诱癌过程中ｃＨａｒａｓ、ｐ２１蛋白、ＡＦＰ及ＰＣＮＡ在肝细胞及肝卵圆细胞中的表达变化。方法：用化学致癌剂３′甲基４二甲基氨偶氮苯（３′ｍｅｔｈｙ１４ｄｉｍｅｔｈｙｌａｍｉｎｏａｚｏｂｅｎｚｅｎｅ，３′ＭｅＤＡＢ）诱发ＳＤ大鼠肝癌，通过免疫组化、原位杂交等方法检测各相关因子在肝细胞及肝卵圆细胞内的表达。结果：诱癌４周，大鼠肝内出现大量的卵圆细胞，呈ＰＣＮＡ强阳性。６～８周，部分增生的卵圆细胞ｐ２１ｒａｓ及ＡＦＰ阳性反应。原位杂交显示，诱癌的第４～８周，ｃＨａｒａｓ的阳性表达细胞呈逐渐增多趋势；１４周时，ｃＨａｒａｓｍＲＮＡ阳性表达细胞减少；至１７周，所有癌组织内显示ｃＨａｒａｓ基因表达阴性，而癌旁组织内则可见ｒａｓ基因的大量表达。结论：卵圆细胞是宿主受化学致癌剂作用后发生肝癌的始动细胞，与肝癌的发生有着密切的联系。
OBJECTIVE: To observe the changes of c-Ha ras, p21 protein, AFP and PCNA expression in hepatocytes and hepatic oval cells during carcinogenesis. METHODS: SD rat HCC was induced by chemical carcinogen 3′-methy 1 4dimethylaminoazobenzene (3′MeDAB) through immunohistochemistry. Methods such as hybridization were used to detect the expression of each relevant factor in hepatocytes and hepatic oval cells. RESULTS: After 4 weeks of induction, a large number of oval cells appeared in the liver of rats and showed strong PCNA positive results. 6 to 8 weeks, some of the proliferative oval cells p21ras and AFP positive reaction. In situ hybridization showed that at the 4th to 8th week of cancer induction, the positive expression cells of c-Ha-ras showed a gradually increasing trend; at 14 weeks, the positive cells of c-Ha-ras mRNA decreased; by 17 weeks, all the cancer tissues were The expression of c-Ha-ras gene was negative, while the expression of ras gene was found in the para-cancer tissues. Conclusion: Oval cells are the originating cells of liver cancer after the host is acted on by chemical carcinogens, and have a close relationship with the occurrence of liver cancer.