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目的：通过动态观察ｃ－ｍｙｃ、Ｈａ－ｒａｓ和Ｋｉ－ｒａｓ在实验性大鼠肝癌形成过程中的表达变化，探讨上述原癌基因与肝癌发生的关系及其生物学意义。方法：用３＇－Ｍｅ－ＤＡＢ饲喂ＳＤ大鼠，分别于第４，６，８，１４和１７周处死大鼠，取其肝脏，石蜡包埋，并进行核酸原位杂交。结果：在诱癌全过程中，ｃ－ｍｙｃ和Ｈａ－ｒａｓ均为同步表达；在诱癌的早期即可检测到较多ｃ－ｍｙｃ和Ｈａ－ｒａｓ的阳性表达细胞，而Ｋｉ－ｒａｓ的细胞数则很少，且反应强度弱；而诱癌后期，各癌基因ｍＲＮＡ阳性表达细胞均减少；至第１７周，所有癌组织内均显示三种癌基因表达阴性，或仅见个别小癌巢内少数癌细胞呈弱阳性。而癌旁肝组织内却可见三种癌基因的大量表达。结论：ｃ－ｍｙｃ和Ｈａ－ｒａｓ被激活是肝癌发生过程中的早期事件，且二者之间具有协同作用，这种协同作用在肝癌的启动上可能具有重要意义；Ｋｉ－ｒａｓ的激活则发生较晚，可能与促进细胞恶性转化有关。
Objective: To observe the expression changes of c-myc, Ha-ras, and Ki-ras in the process of hepatoma formation in experimental rats, and to explore the relationship between the above oncogenes and the occurrence of hepatocellular carcinoma and its biological significance. METHODS: SD rats were fed with 3’-Me-DAB, and the rats were sacrificed at 4, 6, 8, 14 and 17 weeks, and their livers were embedded in paraffin and subjected to in situ nucleic acid hybridization. Results: Both c-myc and Ha-ras were synchronously expressed in the process of induction of cancer; more positive cells of c-myc and Ha-ras could be detected in the early stage of cancer induction, while the cells of Ki-ras were detected. The number was few, and the reaction intensity was weak. In the later stage of cancer induction, the number of positive cells of each oncogene mRNA was decreased; by the 17th week, all the three cancer tissues showed negative oncogene expression, or only in individual small cancer nests. A few cancer cells are weakly positive. In the para-carcinoma liver tissue, abundant expression of three oncogenes can be seen. CONCLUSION: The activation of c-myc and Ha-ras is an early event in the development of hepatocellular carcinoma, and there is a synergistic effect between them. This synergistic effect may play an important role in the initiation of liver cancer; activation of Ki-ras occurs. Later, it may be related to the promotion of malignant transformation of cells.