Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Gene Expression Analysis of Anticancer Drug Induced Hepatotoxicity Using cDNA Microarray

  • Lee, Gyoung-Jae (Research Institute. Shin-Won Scientific Co., Ltd.) ;
  • Kim, Yang-Suk (Bioinformatics Unit, ISTECH Inc.) ;
  • Jung, Jin-Wook (Department of Biochemistry and Molecular Biology, Hanyang University & Genocheck Co., Ltd) ;
  • Hwang, Seung-Yong (Department of Biochemistry and Molecular Biology, Hanyang University & Genocheck Co., Ltd) ;
  • Park, Joon-Suk (Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University) ;
  • Kang, Kyung-Sun (Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University) ;
  • Lee, Yong-Soon (Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University) ;
  • Chon, Man-Suk (Research Institute. Shin-Won Scientific Co., Ltd.) ;
  • Chon, Kum-Jin (Research Institute. Shin-Won Scientific Co., Ltd.) ;
  • Kang, Jong-Soo (Research Institute. Shin-Won Scientific Co., Ltd.) ;
  • Kim, Dong-Hyean (KIST) ;
  • Park, Young-Keun (Department of Biotechnology and Genetic Engineering Korea University)
  • Published : 2006.06.30
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Abstract

Tamoxifen (TAM), a non-steroidal anti estrogen anticancer drug and chemopreventive agent for breast cancer, have caused cholestasis in liver. The potent hepatocarcinogenicity of this drug has been reported. Methotrexate (MTX) is dihydrofolate reductase inhibitor which interfaces with the synthesis for urine nucleotide and dTMP. And it may cause atrophy, necrosis and steatosis in liver. These two anticancer drug have well-known hepatotoxicity. So, in this study we compare the gene expression pattern of antitumor agent TAM and MTX, using the cDNA microarray. We have used 4.8 K cDNA microarray to identify hepatotoxicity-related genes in 5-week-old male Sprague-Dawley (SD) rats. Confirm the pattern of gene expression, we have used Real time PCR for targeted gene. In the case of MTX, Protease related gene (Ctse, Ctsk) and Protein kinase (Pctk 1) have shown specific expression pattern. And in the case of TAM, apoptosis related gene (Pdcd 8) and signal transduction related gene (kdr) have significantly up regulated during treatment time. Gene related with growth factor, lipid synthesis, chemokins were significantly changed. From the result of this study, the information about influence of TAM and MTX to hepatoxicity will provide.

Keywords

References

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