Doseresponse functional gene analysis by exposure

Authors: MiKyung Song YounJung Kim Mee Song HanSeam Choi JaeChun Ryu

Publish Date: 2011/10/05

Volume: 7, Issue: 3, Pages: 221-

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Abstract

Polycyclic aromatic hydrocarbons PAHs are known as carcinogen and have been studied to show modulation of gene expression by exposure to various PAHs However few studies have been reported on microarray analysis of doseresponse relationships of gene expression patterns For comprehensive examination of doseresponse effects of PAHs on gene expression we elicited the genes which were changed more than 15fold by analysis of gene expression profiles in human hepatocellular carcinoma HepG2 cells exposed for 48 h to nontoxic NT and IC20 doses of 3 different PAHs benzoaanthracene BaA benzokfluoranthene BkF and indeno123cdpyrene IND by using human oligonucleotide chip Transcriptomic profiling shows different gene expression patterns in NT and IC20 exposure groups and shows higher sensitivity to gene alteration in IC20 exposure group than NT group Through the clustering analysis of gene expression profiles we identified 7 up and 3 downregulated NT dose specific genes and 401 up and 562 downregulated IC20 dose specific genes After Gene Ontology GO analysis on IC20 dose specific genes we determined several key pathways which are known as related to increase hepatotoxicity such as metabolism of xenobiotics by cytochrome P450 JakSTAT signaling pathway cytokinecytokine receptor interaction and complement and coagulation cascade But we did not find hepatotoxicityrelated pathways through GO analysis on NT dosespecific genes Genes that are expressed in only IC20 exposure group were regarded as biomarker of PAHsinduced hepatotoxicity In conclusion this study describes changes in gene expression profiles in hepatocytes in response to exposure to 3 PAHs with different doses and relates these gene expression changes to hepatotoxicity related pathways Moreover potential new leads to genes and pathways that could play a role in liver disease prevention by PAHs were identified

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