Gene Expression Profiling of 6-MP (6-mercaptopurine) in Liver.
- Author:
Hyung Lae KIM
1
;
Han Na KIM
;
Eun Ju LEE
Author Information
1. Department of Biochemistry, College of Medicine, Ewha Womans University, Seoul, Korea. hyung@ewha.ac.kr
- Publication Type:Original Article
- Keywords:
6-Mercaptopurine (6-MP);
acute hepatoxicity;
microarray analysis;
gene expression
- MeSH:
Adenosine Triphosphate;
Animals;
Cell Death;
Gene Expression Profiling*;
Gene Expression*;
Genome;
Leukemia;
Lipid Metabolism;
Liver*;
Mice;
Microarray Analysis;
Oxidative Stress;
Toxicogenetics;
Toxicology;
Biomarkers
- From:Genomics & Informatics
2006;4(1):16-22
- CountryRepublic of Korea
- Language:English
-
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.
