Gene expression analysis identifies potential biomarkers of phenanthrene in human hepatocytes (HepG2)

Kim

et al. 2011

Mol. Cell. Toxicol.

Self Cite

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 IC 20 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 IC 20 exposure groups and shows higher sensitivity to gene alteration in IC 20 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 downregulated IC 20 dose specific genes. After Gene Ontology (GO) analysis on IC 20 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 IC 20 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.

Section: Discussionsupporting

confidence: 64%

Dose-response functional gene analysis by exposure to 3 different polycyclic aromatic hydrocarbons in human hepatocytes

Kim

et al. 2011

Mol. Cell. Toxicol.

Self Cite

“…We have investigated the mechanism(s) of toxicity of PAHs and other environmental toxicants in human cell lines, based on alteration of gene expression. ( 25,26 ) In this study, we identified gene expression profiles induced by three PAHs in HepG2 cells using a 44K whole human oligonucleotide microarray. With a statistical cut‐off of ≥1.5‐fold change, the expression levels of 532 genes were commonly upregulated and those of 742 genes were commonly downregulated upon exposure to B[a]A, B[k]F, and IND (Fig.…”

Section: Discussionmentioning

confidence: 99%

Polycyclic aromatic hydrocarbons induce migration in human hepatocellular carcinoma cells (HepG2) through reactive oxygen species‐mediated p38 MAPK signal transduction

et al. 2011

Self Cite

Although polycyclic aromatic hydrocarbons (PAHs) are carcinogenic and have been extensively studied with regard to tumor formation, few studies have investigated the involvement of these environmental chemicals in tumor migration and invasion. Polycyclic aromatic hydrocarbons induce reactive oxygen species (ROS) and activate MAPK signal transduction. The p38 signaling transduction pathway, one of the most typical MAPK pathways, plays an essential role in regulating cell migration. Therefore, we investigated whether three PAHs, benzo Reactive oxygen species generation and p38 MAPK activity both increased in a dose-dependent manner and were prevented by SB203580, an inhibitor of p38 MAPK, and N-acetylcysteine (NAC), a ROS scavenger. Expression of migration-related genes was also increased by B[a]A, B[k]F, and IND in a dose-dependent manner and was inhibited by SB203580 and NAC. The migration of HepG2 cells, observed using the Transwell migration assay, also increased in a dose-dependent manner and was prevented by SB203580 and NAC. Our results indicate that the ROS-mediated p38 MAPK signaling pathway plays an essential role in the PAH-induced migration

“…Octanal concentrations were considered appropriate for microarray analysis due to the fact that such an exposure level gives meaningful outcomes in in vitro toxicogenomic studies on carcinogenesis and other toxicity in our research group. 36,43 Our results focused on microarray data, which indicated differential expression of inflammatory response genes after octanal exposure. Aldehyde-induced alterations in stress-responsive genes in the human respiratory system have been studied, 44 but the data regarding changes in cytokine expression are limited.…”

Section: Discussionmentioning

confidence: 99%

Octanal-induced inflammatory responses in cells relevant for lung toxicity

Choi

et al. 2013

Hum Exp Toxicol

Inhalation is an important route of aldehyde exposure, and lung is one of the main targets of aldehyde toxicity. Octanal is distributed ubiquitously in the environment and is a component of indoor air pollutants. We investigated whether octanal exposure enhances the inflammatory response in the human respiratory system by increasing the expression and release of cytokines and chemokines. The effect of octanal in transcriptomic modulation was assessed in the human alveolar epithelial cell line A549 using oligonucleotide arrays. We identified a set of genes differentially expressed upon octanal exposure that may be useful for monitoring octanal pulmonary toxicity. These genes were classified according to the Gene Ontology functional category and Kyoto Encyclopedia of Genes and Genomes analysis to explore the biological processes related to octanal-induced pulmonary toxicity. The results show that octanal affects the expression of several chemokines and inflammatory cytokines and increases the levels of interleukin 6 (IL-6) and IL-8 released. In conclusion, octanal exposure modulates the expression of cytokines and chemokines important in the development of lung injury and disease. This suggests that inflammation contributes to octanal-induced lung damage and that the inflammatory genes expressed should be studied in detail, thereby laying the groundwork for future biomonitoring studies.