Since the first experimental hepatocellular carcinoma by Sasaki and Yoshida, the point of interest in hepatocarcinogenesis has been focused on the nature of precancerous lesions and the way of transformation to carcinoma. However, the exact pathogenetic mechanism and the essential events in malignant transformation of the lesions remain controversial.
The present study is aimed to observe morphologic changes of precancerous lesions and evaluate their nature.
A total of 42 Sprague-Dawley male rats were used for the experiment, and divided into four groups:
(Ⅰ) Normal control group, (Ⅱ) 2-Acetylaminofluorene(AAF) treated group, (Ⅲ) Diethylnitrosamine(DEN)administered group and (Ⅳ)AAF administered group after DEN treatment.
DEN was given intraperitoneally at a dose of 200㎎/㎏. AAF suspended in corn oil was administered through nasogastric tube during 30 days.
Animals were sacrificed at the 7,14,16,20,24,44 and 105th day after administration of AAF. At the time of sacrifice, blood samples were obtained to measure serum SGOT, SGPT, and total protein.
For the morphological examination, right lobe of the liver was remover.
The results are as follows:
1. Both group, one is AAF-administered group and another is AAF-administered group after DEN treatment, showed proliferation of oval cells starting in the periportal tract and later on, development of hyperplastic nodules.
2. After discontinuation of AAF, hyperplastic nodules were disappeared. At the 105th day of the experiment, the liver was still nodular, but underwent architectural remodelling to normal appearing liver.
3. In comparison to AAF-administered group, AAF administered group after DEN treatment produced more hyperplastic nodules in a shorter period of time.
4. The cholangiofibrosis known as a precancerous lesion induced by DAB, was not produced by either DEN or AAF.
Based on these results, it is concluded that hepatocarcinogenesis consists of several steps of precancerous lesion, such as proliferation of oval cells and formation of hyperplastic nodules. The hyperplastic nodule is a reversible lesion and not the final step of procancerous change in hepatocarcinogenesis.
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