Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Gene Expression Profiling in Diethylnitrosamine Treated Mouse Liver: From Pathological Data to Microarray Analysis

Diethylnitrosamine 처리 후 병리학적 결과를 기초로 한 마우스 간에서의 유전자 발현 분석

  • Kim, Ji-Young (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Yoon, Seok-Joo (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Park, Han-Jin (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Kim, Yong-Bum (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Cho, Jae-Woo (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Koh, Woo-Suk (Korea Institute of Toxicology, Korea Research Institute of Chemical Technology) ;
  • Lee, Michael (Department of Biology, College of Natural Sciences, University of Incheon)
  • 김지영 (한국화학연구원 부설 안전성평가연구소) ;
  • 윤석주 (한국화학연구원 부설 안전성평가연구소) ;
  • 박한진 (한국화학연구원 부설 안전성평가연구소) ;
  • 김용범 (한국화학연구원 부설 안전성평가연구소) ;
  • 조재우 (한국화학연구원 부설 안전성평가연구소) ;
  • 고우석 (한국화학연구원 부설 안전성평가연구소) ;
  • 이미가엘 (시립인천대학교 자연과학대학 생물학과)
  • Published : 2007.03.31
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Abstract

Diethylnitrosamine (DEN) is a nitrosamine compound that can induce a variety of liver lesions including hepatic carcinoma, forming DNA-carcinogen adducts. In the present study, microarray analyses were performed with Affymetrix Murine Genome 430A Array in order to identify the gene-expression profiles for DEN and to provide valuable information for the evaluation of potential hepatotoxicity. C57BL/6NCrj mice were orally administered once with DEN at doses of 0, 3, 7 and 20 mg/kg. Liver from each animal was removed 2, 4, 8 and 24 hrs after the administration. The histopathological analysis and serum biochemical analysis showed no significant difference in DEN-treated groups compared to control group. Conversely, the principal component analysis (PCA) profiles demonstrated that a specific normal gene expression profile in control groups differed clearly from the expression profiles of DEN-treated groups. Within groups, a little variance was found between individuals. Student's t-test on the results obtained from triplicate hybridizations was performed to identify those genes with statistically significant changes in the expression. Statistical analysis revealed that 11 genes were significantly downregulated and 28 genes were upregulated in all three animals after 2 h treatment at 20 mg/kg. The upregulated group included genes encoding Gdf15, JunD1, and Mdm2, while the genes including Sox6, Shmt2, and SIc6a6 were largely down regulated. Hierarchical clustering of gene expression also allowed the identification of functionally related clusters that encode proteins related to metabolism, and MAPK signaling pathway. Taken together, this study suggests that match with a toxicant signature can assign a putative mechanism of action to the test compound if is established a database containing response patterns to various toxic compounds.

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References

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