Activation of inflammation/NF-kappaB signaling in infants born to arsenic-exposed mothers.
Activation of inflammation/NF-kappaB signaling in infants born to arsenic-exposed mothers.
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DOI：
10.1371/journal.pgen.0030207
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发表时间：
2007-11
期刊：
影响因子：
4.5
通讯作者：
Samson LD
中科院分区：
文献类型：
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作者：
Fry RC;Navasumrit P;Valiathan C;Svensson JP;Hogan BJ;Luo M;Bhattacharya S;Kandjanapa K;Soontararuks S;Nookabkaew S;Mahidol C;Ruchirawat M;Samson LD
产前暴露于砷的长期健康结果与人口死亡率增加有关。在这项研究中，母亲砷暴露影响新生儿基因表达的程度得到解决。我们监测了母亲在怀孕期间经历不同水平砷暴露的新生儿群体的基因表达谱。通过应用基于机器学习的两类预测算法，我们确定了未暴露于砷和暴露于砷的母亲所生婴儿的表达特征，这些特征高度预测了随后测试人群中的产前砷暴露。此外，11个转录本被确定为捕获的最大预测能力，产前砷暴露分类。砷调节的转录本的网络分析确定了广泛的分子网络的激活，这些分子网络指示新生儿中的应激、炎症、金属暴露和细胞凋亡。在美国和世界各地，接触砷是一种重要的健康危害，并与几种癌症和其他慢性疾病的风险增加有关。这些研究清楚地表明了母亲的砷消费对胎儿基因表达的强大影响，正如新生儿脐带血中的转录水平所证明的那样。砷是一种环境污染物和已知的人类致癌物。长期接触砷污染的水是全世界包括美国在内的一个重要的公共卫生危害，数百万人接触的饮用水的水平远远超过世界卫生组织（世卫组织）的准则。鉴于产前暴露对人类健康的影响和已知的慢性砷暴露的公共卫生危害，本研究旨在确定母体砷暴露在人群中影响新生儿基因表达的程度。作者表明，人类产前砷暴露会导致新生儿惊人的基因表达变化。在怀孕期间暴露于砷的母亲所生的婴儿中监测到的基因表达变化高度预测了随后的测试人群中的产前砷暴露。这项研究建立了一个只有11个转录本的子集，这些转录本具有最大的预测能力，可以证明它们是有希望作为产前砷暴露的遗传生物标志物。对子宫内暴露于砷的婴儿的全基因组反应的通路分析表明，涉及NF-κB、炎症、细胞增殖、应激和凋亡的整合通路网络被强烈激活。这项研究有助于我们了解砷暴露的生物反应。
The long-term health outcome of prenatal exposure to arsenic has been associated with increased mortality in human populations. In this study, the extent to which maternal arsenic exposure impacts gene expression in the newborn was addressed. We monitored gene expression profiles in a population of newborns whose mothers experienced varying levels of arsenic exposure during pregnancy. Through the application of machine learning–based two-class prediction algorithms, we identified expression signatures from babies born to arsenic-unexposed and -exposed mothers that were highly predictive of prenatal arsenic exposure in a subsequent test population. Furthermore, 11 transcripts were identified that captured the maximal predictive capacity to classify prenatal arsenic exposure. Network analysis of the arsenic-modulated transcripts identified the activation of extensive molecular networks that are indicative of stress, inflammation, metal exposure, and apoptosis in the newborn. Exposure to arsenic is an important health hazard both in the United States and around the world, and is associated with increased risk for several types of cancer and other chronic diseases. These studies clearly demonstrate the robust impact of a mother's arsenic consumption on fetal gene expression as evidenced by transcript levels in newborn cord blood. Arsenic is an environmental pollutant and known human carcinogen. Chronic exposure to arsenic-contaminated water is an important public health hazard around the world, including the United States, with millions exposed to drinking water with levels that far exceed World Health Organization (WHO) guidelines. Given the implications of prenatal exposure on human health and the known public health hazard of chronic arsenic exposure, this study was aimed at establishing the extent to which maternal arsenic exposure in a human population affects newborn gene expression. The authors show that prenatal arsenic exposure in a human population results in alarming gene expression changes in newborn babies. The gene expression changes monitored in babies born to mothers exposed to arsenic during pregnancy are highly predictive of prenatal arsenic exposure in a subsequent test population. The study establishes a subset of just 11 transcripts that captured maximal predictive capability that could prove promising as genetic biomarkers of prenatal arsenic exposure. Pathway analysis of the genome-wide response in the babies exposed to arsenic in utero indicates robust activation of an integrated network of pathways involving NF-κB, inflammation, cell proliferation, stress, and apoptosis. This study contributes to our understanding of biological responses to arsenic exposure.