Analysis of the toxicogenomic effects of exposure to persistent organic pollutants (POPs) in Slovakian girls: correlations between gene expression and disease risk.
Analysis of the toxicogenomic effects of exposure to persistent organic pollutants (POPs) in Slovakian girls: correlations between gene expression and disease risk.
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分析斯洛伐克女孩中暴露于持续的有机污染物（POP）的毒物基因组作用：基因表达与疾病风险之间的相关性。
DOI：
10.1016/j.envint.2011.09.003
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发表时间：
2012-02
影响因子：
11.8
通讯作者：
Dutta SK
中科院分区：
文献类型：
--
作者：
Mitra PS;Ghosh S;Zang S;Sonneborn D;Hertz-Picciotto I;Trnovec T;Palkovicova L;Sovcikova E;Ghimbovschi S;Hoffman EP;Dutta SK
世界各地环境中持久性有机污染物（POPs）的化学成分并不统一，这些污染物含有许多结构不同的亲脂性化合物。在斯洛伐克共和国的一个明确的研究队列中，对暴露儿童外周血中存在的持久性有机污染物化学物质进行了化学分析。化学分析数据显示结构不同的有机污染物的相对浓度和分布，包括多氯联苯（PCB）、2,2'-双（4-氯苯基）-1,1-二氯乙烯（p,p'-DDE）、2,2'-双（4-氯苯基）-1,1,1-三氯乙烷（p,p'-DDT）、 即使在同一暴露区域内，六氯苯 (HCB) 和 β-六氯环己烷 (β-HCH) 的含量也可能因人而异。这些化学品可大致分为两类。第一组是 PCB 同系物，主要源自工业化合物及其副产品。第二组化合物源自农业部门或在农业部门中常用（例如 DDT、HCB）。本研究的目的是检查两种 POP 暴露情况对基因表达的影响。对于研究人群，我们选择了血液中 POP 浓度较高（> POP 总量的 75%）的青春期前女孩（平均年龄 46.2 ± 1.4 个月），当 PCB 总浓度显着高于其他 POP 成分的总浓度时，将她们分类为高“PCB”组；当 PCB 总浓度显着低于其他主要 POP 成分的浓度时，将她们分类为“非 PCB”(OTP) 组 选民。选择匹配的女孩对照组（< POP 总数的 25%）用于比较目的（每组 n = 5）。我们的目的是确定高 POP 暴露在毒理基因组水平上是否存在任何共同影响，并研究暴露如何在两种不同的暴露情况下影响儿童的生理功能。使用微阵列（Affymetrix Gene Chip Human Genome U133 Plus 2.0 Array）平台对女孩外周血单个核细胞的总 RNA 进行整体基因表达分析。结果由密歇根州路易斯市的 Partek GS 进行分析，鉴定出 12 个基因（ATAD2B、BIVM、CD96、CXorf39、CYTH1 ETNK1、FAM13A、HIRA、INO80B、ODG1、RAD23B 和 TSGA14）和两个未识别的探针组，这些基因在 PCB 和 OTP 组中与对照组有差异性调节。 qRT-PCR方法用于验证微阵列结果。 Ingenuity Pathway Analysis (IPA) 软件包确定了与每个基因组相关的可能的分子损伤和疾病风险。结缔组织疾病、遗传疾病、骨骼肌疾病和神经系统疾病与这12个常见基因有关。因此，这些数据确定了 POP 暴露在基因组水平上的潜在分子影响。本报告强调了进一步研究的重要性，以验证随机人群的结果，并评估已确定的基因作为 POP 暴露生物标志物的用途。
The chemical composition of Persistent Organic Pollutants (POPs) in the environment is not uniform throughout the world, and these contaminants contain many structurally different lipophilic compounds. In a well-defined study cohort in the Slovak Republic, the POP chemicals present in the peripheral blood of exposed children were chemically analyzed. The chemical analysis data revealed that the relative concentration and profile of structurally different organic pollutants, including polychlorinated biphenyls (PCBs), 2,2’-bis(4-chlorophenyl)-1,1- dichloroethylene (p,p’-DDE), 2,2’-bis(4-chlorophenyl)-1,1,1-trichloro-ethane (p,p’-DDT), hexachlorobenzene (HCB) and β-hexachlorocyclohexane (β-HCH), may vary from individual to individual, even within the same exposure area. These chemicals can be broadly classified into two groups. The first group, the PCB congeners, primarily originated from industrial compounds and their byproducts. The second group of compounds originated from or was commonly used in the agricultural sector (e.g., DDT, HCB). The objective of this study was to examine the effects of the two POP exposure profiles on gene expression. For the study population, we selected prepubertal girls (mean age of 46.2 ± 1.4 months) with high POP concentrations in their blood (> 75% tile of total POP) and classified them in the high ‘PCB’ group when the total PCB concentration was significantly higher than the total concentration of other POP components and in the ‘Other Than PCB’ (OTP) group, when the total PCB concentration was significantly lower than the concentration of the other major POP constituents. A matched control group of girls (< 25% tile of total POP) was selected for comparison purpose (n = 5 per group). Our aims were to determine whether there were any common effects of high POP exposure at a toxicogenomic level and to investigate how exposure may affect physiological functions of the children in two different exposure scenarios. Global gene expression analysis using a microarray (Affymetrix Gene Chip Human genome U133 Plus 2.0 Array) platform was conducted on the total RNA of peripheral blood mononuclear cells from the girls. The results were analyzed by Partek GS, Louis, MI, which identified twelve genes (ATAD2B, BIVM, CD96, CXorf39, CYTH1 ETNK1, FAM13A, HIRA, INO80B, ODG1, RAD23B, and TSGA14) and two unidentified probe sets, as regulated differentially in both the PCB and OTP groups against the control group. The qRT-PCR method was used to validate the microarray results. The Ingenuity Pathway Analysis (IPA) software package identified the possible molecular impairments and disease risks associated with each gene set. Connective tissue disorders, genetic disorders, skeletal muscular disorders and neurological diseases were associated with the 12 common genes. The data therefore identified the potential molecular effects of POP exposure on a genomic level. This report underscores the importance of further study to validate the results in a random population and to evaluate the use of the identified genes as biomarkers for POP exposure.