PDGF-Rα Expression in Preneoplastic and Neoplastic Hepatocellular Lesions: A Rat Model N-nitrosomorpholine Stop Experiment
김수진, 김경태, 정진숙,
소속 상세정보
김수진 ( Kim Soo-Jin )
동아대학교 의과대학 병리학교실
김경태 ( Kim Kyoung-Tae )
동아대학교 의과대학 내과학교실
정진숙 ( Jeong Jin-Sook )
동아대학교 의과대학 병리학교실
KMID : 0357920060400050354
Abstract
Background: N-nitrosomorpholine (NNM) is a genotoxic hepatocarcinogenic agent. Preneoplastic and neoplastic hepatocyte lesions were induced in rats by oral exposure to NNM (200 mg/L) in a stop model experiment. Platelet-derived growth factor receptor (PDGF-R) is a tyrosine kinase receptor that works with PDGF, stimulating cellular growth and proliferation. The present study was designed to determine the role of PDGF-Rα expression in hepatocellular neoplasms and precursors.
Methods: Seventeen rats out of a starting number of 30 died. From the fifth week until the 24th week one or two rats were evaluated. Preneoplastic single cells or foci, foci of altered hepatocytes (FAH) hepatocellular adenomas (HCA) and hepatocellular carcinomas (HCC) were studied histologically, and the expressions of GSTp and PDGF-Rα by immunohistochemistry.
Results: At the fifth week, GSTp+ single cells showed PDGF-Rα expression (20.8±5.8%). At the sixth week, GSTp+ single cells, located at periportal areas, co-expressed PDGF-Rα (43.4±9.6%). Over the next several weeks periportal hepatocytes showed weaker PDGF-Rα expression but no GSTp. GSTp+ FAH, and all HCA, demonstrated no PDGF-Rα expression. However, nine out of 10 (90%) HCC showed PDGF-Rα expression.
Conclusions: These data showed that there were two peaks of PDGF-Rα expression, and suggest that the earlier expression is related with the response to NNM-induced hepatocyte toxicity, and that the later response is associated to malignant transformation.
키워드
N-nitrosomorpholine;Rat liver;PDGF receptor;Malignant transformation
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