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KMID : 1034820060020020144
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Molecular & Cellular Toxicology
2006 Volume.2 No. 2 p.144 ~ p.149
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Gene Expression Analysis of Anticancer Drug Induced Hepatotoxicity Using cDNA Microarray
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Lee Gyoung-Jae
Kim Yang-Suk
Jung Jin-Wook
Hwang Seung-Yong
Park Joon-Suk
Kang Kyung-Sun
Lee Yong-Soon
Chon Man-Suk
Chon Kum-Jin
Kang Jong-Soo
Kim Dong-Hyean
Park Young-Keun
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Abstract
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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.
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KEYWORD
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Toxicogenomics, Antitumor agent, Hepatotoxicity, Microarray, Hepatocarcinogenesis
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