Genomics Inform.  2006 Mar;4(1):16-22.

Gene Expression Profiling of 6-MP (6-mercaptopurine) in Liver

Affiliations
  • 1Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, Korea. hyung@ewha.ac.kr

Abstract

The KFDA (Korea Food & Drug Administration) has performed a collaborative toxicogenomics project since 2003. Its aim is to construct a toxicology database of 12 compounds administered to mice at initial phase. We chose 6-MP (6-mercaptopurine) which has been used in the treatment of childhood leukemia. It was administered at low (0.224 mg/kg) and at high (2.24 mg/kg) dose (5 mice per group) intraperitonealy to the postnatal 6 weeks mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after scarification. 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. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to 6-MP induced toxicity, including lipid metabolism abnormality, inflammatory response, oxidative stress, ATP depletion and cell death. The potential toxic effects appearing as gene expression changes are dependent of the time of 6-MP but independent of the dosage of it. This study would contribute to establishment of international database as well as national one about hepatotoxicity.

Keyword

6-Mercaptopurine (6-MP); acute hepatoxicity; microarray analysis; gene expression

MeSH Terms

Adenosine Triphosphate
Animals
Cell Death
Gene Expression Profiling*
Gene Expression*
Genome
Leukemia
Lipid Metabolism
Liver*
Mice
Microarray Analysis
Oxidative Stress
Toxicogenetics
Toxicology
Biomarkers
Adenosine Triphosphate
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