• Title/Summary/Keyword: toxicogenomics

Search Result 308, Processing Time 0.975 seconds

Toxicogenomics Study on ${\alpha}-Naphthylisothiocyanate\;(ANIT)$ Induced Hepatotoxictiy in Mice

  • Hwang, Ji-Yoon;Lim, Jung-Sun;Jeong, Sun-Young;Park, Han-Jin;Cho, Jae-Woo;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
    • /
    • v.2 no.1
    • /
    • pp.48-53
    • /
    • 2006
  • [ ${\alpha}-Naphthylisothiocyanate$ ] (ANIT) induces intrahepatic cholestasis, involving damage to biliary epitheial cells. This study investigates hepatic gene expression and histopathological alterations in response to ANIT treatment in order to elucidate early time response of ANIT-induced hepatotoxicity. ANIT was treated with single dose (3, 6, and 60 mg/kg) in corn oil by oral gavage. Serum biochemical and histopathological observation were performed for evaluation of hepatotoxicity level. Affymetrix oligo DNA chips were used for gene expression profile by ANIT-induced hetpatoxicity. Hepatic enzyme levels (ALT, AST, and ALP) were increased in 24 hr high dose group. In microscopic observations, moderate hepatocellular necrosis, were confirmed 24 hr high dose groups. We found that gene expression patterns were dependent on time and dose. Our selected genes were related inflammation and immunomodulation. In this study, ANIT-induced hepatotoxicity was involved in acute phase responses and provides evidence for role of neutrophil could be mechanism associated with ANIT-mediated hepatotoxicity.

Toxicogenomics Analysis on Thioacetamide-induced Hepatotoxicity in Mice

  • Lim, Jung-Sun;Jeong, Sun-Young;Hwang, Ji-Yoon;Park, Han-Jin;Cho, Jae-Woo;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
    • /
    • v.2 no.2
    • /
    • pp.126-133
    • /
    • 2006
  • Thioacetamide (TA) is well known hepatotoxic and hepatocarcinogenic agent. TA also diminishes the contents of hepatic cytochrome P450 and inhibits the enzyme activity of the hepatic mixed function oxidases. TA metabolite, thioacetamide-s-oxide, is further transformed into a still unknown highly reactive metabolite that binds to macromolecules. In this study, we focused on TA-induced gene expression at hepatotoxic dose. Mice were exposed to two levels (5 mg/kg or 50 mg/kg i.p.) of TA, sampled at 6 or 24 h, and hepatic gene expression levels were determined to evaluate dose and time dependent changes. We evaluated hepatotoxicity by serum AST and ALT level and histopathological observation. Mean serum activities of the liver leakage enzymes, AST and ALT, were slightly increased compare to control. H & E and PAS evaluation of stained liver sections revealed TA-associated histopathological finding in mice. Centrilobular eosinophilic degeneration was observed at high dose-treated mice group. Hepatic gene expression was analyzed by QT clustering. Clustering of high dose-treated samples with TA-suggests that gene expressional changes could be associated from toxicity as measured by traditional biomarkers in this acute study.

Enu is a Powerful Mutagen for Development Mutant Mice -Sixty-Six Mutants From Enu Mutagenesis Program in Kit/Krict-

  • Seokjoo Yoon;Cho, Kyu-Hyuk;Cho, Jae-Woo;Lee, Phil-Soo;Kim, Yang-Eon;Cha, Dal-Sun;Park, Han-Jin;Kang, Min-Sung;Nam, Yoon-Yi
    • Proceedings of the Korean Society of Toxicology Conference
    • /
    • 2003.10b
    • /
    • pp.184-184
    • /
    • 2003
  • ENU(ethylnitrosourea) mutagenesis has been carrying out since 1999 in Korea Institute of Toxicology (KIT), Korea Research Institute Chemical of Technology (KRlCT). We have chosen BALB/c and C57BL/6 and screened for dominant and recessive mutants. Four hundred and twenty one males(GO) have been injected with ENU, 150, 200, 250 and 300 mg/kg body weight, twice, one week apart.(omitted)

  • PDF

XPERNATO-TOX: an Integrated Toxicogenomics Knowledgebase

  • Woo Jung-Hoon;Kim Hyeoun-Eui;Kong Gu;Kim Ju-Han
    • Genomics & Informatics
    • /
    • v.4 no.1
    • /
    • pp.40-44
    • /
    • 2006
  • Toxicogenomics combines transcriptome, proteome and metabolome profiling with conventional toxicology to investigate the interaction between biological molecules and toxicant or environmental stress in disease caution. Toxicogenomics faces the problems of comparison and integration across different sources of data. Cause of unusual characteristics of toxicogenomic data, researcher should be assisted by data analysis and annotation for getting meaningful information. There are already existing repositories which claim to stand for toxicogenomics database. However, those just contain limited abilities for toxicogenomic research. For supporting toxicologist who comes up against toxicogenomic data flood, now we propose novel toxicogenomics knowledgebase system, XPERANTO-TOX. XPERANTO-TOX is an integrated system for toxicogenomic data management and analysis. It is composed of three distinct but closely connected parts. Firstly, Data Storage System is for reposit many kinds of '-omics' data and conventional toxicology data. Secondly, Data Analysis System consists of analytical modules for integrated toxicogenomics data. At last, Data Annotation System is for giving extensive insight of data to researcher.

Gene Expression Analysis of Hepatic Response Induced by Gentamicin in Mice

  • Oh, Jung-Hwa;Park, Han-Jin;Hwang, Ji-Yoon;Jeong, Sun-Young;Lim, Jung-Sun;Kim, Yong-Bum;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
    • /
    • v.3 no.1
    • /
    • pp.60-67
    • /
    • 2007
  • Gentamicin is a broad-spectrum aminoglycoside antibiotic used in the treatment of bacterial infection. Although side effects of gentamicin such as nephrotoxicity and ototoxicity have been investigated, the information on the hepatic effects of gentamicin is still limited. In the present study, gene expression profiles were analyzed in the liver of gentamicin treated mice using Affymetrix GeneChip$^{(R)}$ Mouse Expression 430A 2.0 Array. Totally, 400 genes were identified as being either up- or down-regulated over 1.5-fold changes (P<0.01) in the liver of gentamicin treated mice. Among these deregulated genes, 16 up-regulated genes mainly involved in transport (Kif5b, Pex14, Rab14, Clcn3, and Necap1) and 20 down-regulated genes involved in lipid and other metabolisms (Hdlbp, Gm2a, Uroc1, and Dak) were selected using k-means clustering algorithm. The functional classification of differentially expressed genes represented that several stress-related genes were regulated in the liver by gentamicin treatment. This data may contribute in understanding the molecular mechanism in the liver of gentamicin treated mice.