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KMID : 0379520060220020087
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한국독성학회지
2006 Volume.22 No. 2 p.87 ~ p.93
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Gene Expression Analysis of Phenylbutazone-induced Liver Damage in Mice
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Lee Eun-Ju
Jeong In-Hye
Kim Han-Na
Chung Hee-Kyoung
Kong Gu
Kang Kyung-Sun
Yoon Byung-Il
Lee Byung-Hoon
Lee Mi-Ock
Kim Joo-Han
Kim Hyung-Rae
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Abstract
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The KFDA (Korea Food & Drug Administration) has performed a collaborative toxico-genomics project since 2003. Its aim is to construct a toxicologenomic database of 12 hepatotoxic compounds from mice livers. Phenylbutazone which is non-steroidal anti-inflammatory drug was assigned. It was administered at low (0.0238 mg/kg) and at high (0.238 mg/kg) dose (5 mice per group) orally to the postnatal 6 weeks ICR mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after administration. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. The 2-way ANOVA was used to find genes that reflected phenylbutazone-induced acute toxicity or dose-dependant changes. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to phenylbutazone induced toxicity, including lipid metabolism abnormality, oxidative stress, cell death and cytoskeleton destruction.
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KEYWORD
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Phenylbutazone, drug toxicity, microarray analysis, gene expression profiling
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