Dynamic Changes of JNK1 During Hepatocarcinogenesis Induced by Aflatxin B1 in Rats

Objective To explore the significance of JNK signal transduction pathway in HCC and its effects on develoment of HCC. Methods Total 77 male SD rats were randomly divided into two groups: The experimental group included 66 rats and were administered with AFB1 by intraperitoneal injection for 32 weeks. Whereas, 11 rats was not administered with AFB1 and served as control group. All animals in 12th week, 20th week, 36th week, 46th week and 58th week were detected by biopsy. All survivals were sacrificed in 58th week. All liver tissues were studied by Routine Mayer's Hematoxylin and Eosin Stain (H&E), mRNA level of JNK1 genes and the activity of phosphorylation JNK1 were determined by RT-PCR and western blot respectively. Results The first HCC case was discovered in 46th week. 24 cases rats developed HCC and were alive at the end of experiment (58th week) among the AFB1-treated animals, 6 rats didn't have any carcinoma. No tumor was developed in the control group animals. The mRNA of JNK1 gene was found in all of liver tissues, the expression level of JNK1 mRNA in HCC tissues was higher than that in para-HCC liver tissues and higher than that in biopsy liver tissues（P<0.05）. The data of western blot showed that the p-JNK1 can be detected in experimental group, the earliest positive time of p-JNK1 were 36th week and 20th week in HCC developed and no HCC developed rat respectively. The positive rate of p-JNK1 increased in the AFB1-treated time-dependent manner（P>0.05）. The semiquantitative analysis data showed that the quantity of p-JNK1 in liver tissues from not HCC developed rats is higher than that in liver tissues and HCC tissues form HCC developed rats（P<0.01）. Conclusion The data from the AFB1-treated experimental rat models show that the JNK signal transduction pathway is activated in liver tissues and that this activation contributes to inhibit HCC development.