Song, Mi-Kyung Kim, Youn-Jung Song, Mee Choi, Han-Seam Ryu, Jae-Chun 2024-01-20T16:05:15Z 2024-01-20T16:05:15Z 2021-09-05 2011-09-30 1738-642X https://pubs.kist.re.kr/handle/201004/129971 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 dose-response relationships of gene expression patterns. For comprehensive examination of dose-response effects of PAHs on gene expression, we elicited the genes which were changed more than 1.5-fold 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 (benzo[a]anthracene (B[a]A), benzo[k]fluoranthene (B[k]F) and indeno[1,2,3-c,d]pyrene (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 down-regulated NT dose specific genes and 401 up- and 562 down-regulated 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, Jak-STAT signaling pathway, cytokine-cytokine receptor interaction and complement and coagulation cascade. But we did not find hepatotoxicity-related pathways through GO analysis on NT dose-specific genes. Genes that are expressed in only IC20 exposure group were regarded as biomarker of PAHs-induced 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. English KOREAN SOCIETY TOXICOGENOMICS & TOXICOPROTEOMICS-KSTT ACTIVATABLE FIBRINOLYSIS INHIBITOR EXPRESSION TOXICOGENOMICS DISCRIMINATION IDENTIFICATION Dose-response functional gene analysis by exposure to 3 different polycyclic aromatic hydrocarbons in human hepatocytes Article 10.1007/s13273-011-0028-7 1 MOLECULAR & CELLULAR TOXICOLOGY, v.7, no.3, pp.221 - 232 MOLECULAR & CELLULAR TOXICOLOGY 7 3 221 232 scie scopus kci other ART001661219 000295546000003 2-s2.0-84863077087 Biochemistry & Molecular Biology Toxicology Biochemistry & Molecular Biology Toxicology Article ACTIVATABLE FIBRINOLYSIS INHIBITOR EXPRESSION TOXICOGENOMICS DISCRIMINATION IDENTIFICATION Polycyclic aromatic hydrocarbons (PAHs) Benzo[a]anthracene (B[a]A) Benzo[k]fluoranthene (B[k]F) Indeno[1,2,3-c,d]pyrene (IND) Microarray Gene Ontology (GO) Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway Hepatotoxicity