페닐부타존에 의해 간손상이 유발된 생쥐의 유전자 발현 분석

Abstract

The KFDA (Korea Food & Drug Administration) has performed a collaborative toxicogenomics 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.