Changes in gene expression induced by polycyclic aromatic hydrocarbons in the human cell lines HepG2 and A549

Changes in gene expression induced by polycyclic aromatic hydrocarbons in the human cell lines HepG2 and A549
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DOI:
10.1016/j.tiv.2007.10.009
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发表时间:
2008-03-01
影响因子:
3.2
通讯作者:
Albores, Arnulfo
Albores, Arnulfo
中科院分区:
医学3区
文献类型:
--
作者:
Castorena-Torres, Fabiola;de Leon, Mario Bermudez;Albores, Arnulfo

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多环芳烃(PAH)是焦炉工厂排放物的主要成分,其中许多化学品具有致癌性。本研究的目的是研究基因表达的变化,在两个人类细胞系,HepG2和A549,诱导暴露于土壤提取物含有多环芳烃使用微阵列技术。土壤样品是从墨西哥东北部的一个焦炉工厂附近获得的。为了比较,还分析了苯并[a]芘(BaP)诱导的基因表达模式。两种处理的改变基因的数量在肝细胞中比在肺细胞中高2倍。使用基因组数据库,通过生物学功能鉴定和分组两种细胞系中的差异调节基因。一组9个基因的上调和下调的PAH提取物或苯并(a)芘被选择用于实时PCR验证。这些PAH应答基因的细胞功能包括:异源物质代谢(CYP1A1和CYP1B1)、DNA修复(ERCC 5)、氧化应激反应和细胞增殖(FTH 1和PRDX 1)、蛋白质降解(PSMD 7)、离子转运(FXYD 3)、类固醇生物合成(FDFT 1)和信号通路(PTGER 3)。实时荧光PCR分析证实了大部分芯片数据具有显著相关性。需要进一步的研究来确定参与PAH介导的这些基因调节的机制,并将这些变化与人类健康联系起来。(C)2007爱思唯尔有限公司版权所有。
Polycyclic aromatic hydrocarbons (PAH) are the main components of emissions generated by coke oven factories and many of these chemicals are carcinogenic. The goal of this study was to examine changes in gene expression in two human cell lines, HepG2 and A549, induced by exposure to a soil extract containing PAH using microarry technology. Soil samples were obtained from the vicinity of a coke oven factory in northeastern Mexico. For comparison, the gene expression pattern induced by Benz[a]pyrene (BaP) was also analyzed. The number of altered genes by both treatments was 2-fold higher in hepatic than in pulmonary cells. Differentially-modulated genes in the two cell lines were identified and grouped by biological function using genomic databases. A group of nine genes up- and down-regulated by either the PAH extract or BaP were selected for validation by real-time PCR. The cellular functions of these PAH-responsive genes included: xenobiotic metabolism (CYP1A1 and CYP1B1), DNA repair (ERCC5), oxidative stress response and cell proliferation (FTH1 and PRDX1), protein degradation (PSMD7), ion transport (FXYD3), steroid biosynthesis (FDFT1), and signaling pathways (PTGER3). The real-time PCR analysis confirmed most of the microarray data with significant correlation. Additional studies are required to determine the mechanisms involved in the PAH-mediated modulation of these genes and to associate these changes with human health. (C) 2007 Elsevier Ltd. All rights reserved.