Changes of ultrastructure and N-ras gene expression in aflatoxin B1-induced hepatocellular carcinoma in rat model.

Objective To observe the ultrastructural morphology of hepatocytes and study the dynamic changes of mRNA expression of N-ras gene on hepatocellular carcinoma(HCC) induced by aflatoxin B1 (AFB1) in male Wistar rats.Methods The HCC model of male Wistar rats was established by interval intraperitoneal injection of AFB1(400 μg/kg).Ultrastructural morphology of liver tissues was observed by transmission electron microscopy,and mRNA expression of N-ras gene was detected by RT-PCR technology for normal liver tissues,injured liver tissues,early cancerous and HCC liver tissues,respectively.Results A series of characteristic hepatoxic lesion changes were observed during the process of hepatocarcinogenesis in our rat model in cluding occurrences of atypical cells and cancerous cells.Mitochondria proliferated and swelled at early stage of hepatocarcinogenesis,then vanished and altered to vacuole structure at later stage.Hepatin grains were abundant at early stage,but decreased gradually.We also observed that hepatocytes phagocytized other cells during the process of hepatocarcinogenesis.The differences in mRNA expression levels of N-ras were statistically significant between HCC or early cancerous liver tissues and normal livers,and also injured liver tissues(F=5.47,P=0.019 and the latter,F=6.98,P=0.006).Conclusion The hepatoxic lesion,formation of atypical and cancerous cells of hepatocytes were observed during the AFB1 induced process of hepatocarcinogenesis in the rat model.The increased expression of N-ras mRNA may contribute to the pathogenesis of HCC.