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The Korean Journal of Pathology 2001;35(5): 383-390.
Expression of Fas/Fas Ligand and Its Relationship with Apoptosis in Chemically Induced Preneoplastic Lesions in Rat Liver.
Hye Jin Lee, Do Youn Park, Kyung Un Choi, Jee Yeon Kim, Chang Hun Lee, Mee Young Sol, Kang Suek Suh
Departments of Pathology, Pusan National University College of Medicine and Saint Benedict Hospital, Busan 602-739, Korea. pdy220@netsgo.com
ABSTRACT
BACKGROUND: Apoptosis of hepatocytes plays a major role in experimental hepatocarcinogenesis of rats. But sequential change and localization of Fas and Fas ligand (FasL) in preneoplastic lesions and the relationship with apoptosis are not clearly elucidated. METHODS: We investigated sequential change and localization of Fas/FasL and its relationship to apoptosis in preneoplastic lesions of chemical hepatocarcinogenesis in rats using northern blot analysis, immunohistochemistry and terminal deoxynucleotidyl transferase end labeling (TUNEL) assay. RESULTS: We found that mRNA of Fas and Fas ligand increased for up to 42 days and 14 days after partial hepatectomy, respectively, and thereafter decreased with time. Fas protein was localized on the cytoplasm of hepatocytes of preneoplastic lesions, as well as on the cytoplasmic membrane of the adjacent liver parenchyme. Fas negative preneoplastic lesions were evident at 42 days after partial hepatectomy. FasL protein was found only in the cytoplasm of hepatocytes of preneoplastic lesions, instead of in the adjacent liver parenchyme. FasL-positive hepatocytes increased with time for up to 14 days after partial hepatectomy and therafter decreased. Also, TUNEL-positive apoptotic cells increased with time and were more numerous in the adjacent liver parenchyme than in the preneoplastic lesions. CONCLUSIONS: It was suggested that Fas/FasL-mediated apoptosis might be one of the major mechanisms for controlling apoptotic cell death in the promotion stage of chemical hepatocarcinogenesis.
Key Words: Carcinoma; Hepatocarcellular; Antigens; CD95; Apoptosis