1Departments of General Surgery, Dong-A University College of Medicine, Pusan, Korea. sskim@daunet.donga.ac.kr 2Departments of Pathology, Dong-A University College of Medicine, Pusan, Korea. 3Departments of Pharmacology, Dong-A University College of Medicine, Pusan, Korea.
ABSTRACT
PURPOSE: The early carcinogenic effect of N-nitrosomorpholine (NNM) on acquisition of increased survival and growth was investigated using ex vivo culture of 5th to 10th week rat liver hepatocytes after NNM treatment.
MATERIALS AND METHODS: Rats were fed with NNM (200 mg/l).
Hepatocytes were isolated by two step perfusion techniques and grown on tissue culture.
These ex vivo hepatocytes were then subjected to analysis of growth related signal molecules resided in nucleoli.
RESULTS: One of the most characteristic differences of the NNM-treated liver from normal liver was genesis of megahepatocytes. These megahepatocytes survived approximately 2~3 times as long as normal hepatocytes in ex vivo conditions. There was also a significant increase in various nucleolar proteins, including Erk1/2, p38, hsp72 and nucleophosmin (B23).
CONCLUSION: At promotion stage of tumorigenesis induced by NNM, it was possible to isolate and characterize abnormal hepatocytes. These abnormal hepatocytes showed increased survival in in vitro (ex vivo) than normal hepatocytes, although they were not immortal.
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