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KMID : 0043320100330020247
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Archives of Pharmacal Research
2010 Volume.33 No. 2 p.247 ~ p.255
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Evaluation of Plasma Carcinogenic Markers in Rat Hepatic Tumors Models Induced by Rat Hepatoma N1-S1 Cells and Benzo[a]pyrene
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Sul Dong-geun
Park So-Young
Phark So-Hee
Lee Min
Zheng Zhi
Choi Seon-Young
Won Nam-Hee
Jung Woon-Un
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Abstract
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Benzo[a]pyrene (BaP) is a known carcinogen. Grilled or smoked meat is the major source of BaP intake for human beings. Previously, we established hepatic tumor animal models by injecting rat hepatoma N1-S1 cells or concomitant injection of N1-S1 cells and BaP into healthy Sprague-Dawley rats. In this study, we performed proteomic analyses of rat plasma collected from a hepatic tumor model and compared them to controls using a 3-10 pI range and large two dimensional gel electrophoreses. Proteomic analyses of rat plasma with hepatic tumors induced by the injection of N1-S1 cells resolved 1295 protein spots. Among them, 10 proteins were identified by ESI-MS-MS; four proteins were up-regulated and six proteins were down-regulated as compared to the controls. In addition, 1295 protein spots were also resolved from rats with hepatic tumors by the injection of N1-S1 cells plus BaP; five proteins were upregulated, and seven proteins were down-regulated. Of these 12 proteins, 10 proteins were identified by ESI-MS-MS. Out of 20 identified proteins, alpha-1-inhibitor 3 and zero beta-1 globin were down-regulated in both rats with hepatic tumors by N1-S1 cell-only and rats with hepatic tumors by the injection of N1-S1 cell plus BaP as compared to the controls. In addition, the identities of four proteins, including dermcidin, serum amyloid P-component (SAP), proteasome subunit alpha type-4 and glutathione peroxidase 3 (GPX-3) were confirmed by western blot analysis. Therefore, the importance of those proteins as candidate biomarkers for the development of hepatic tumors should be further elucidated.
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KEYWORD
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Benzo[a]pyrene, ESI-MS-MS, Hepatic tumor, N1-S1 Rat hepatoma cells, Protemics, Rat plasma, Two-dimensional polyacrylamide gel electrophoresis
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