Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599.
Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
Exposure to inorganic arsenic (iAs) early in life is associated with adverse health effects in infants, children, and adults, and yet the biological mechanisms that underlie these effects are understudied. The objective of this research was to examine the proteomic shifts associated with prenatal iAs exposure using cord blood samples isolated from 50 newborns from Gómez Palacio, Mexico. Levels of iAs in maternal drinking water (DW-iAs) and the sum of iAs and iAs metabolites in maternal urine (U-tAs) were determined. Cord blood samples representing varying iAs exposure levels during the prenatal period (DW-iAs ranging from <1 to 236 μg As/l) were analyzed for altered expression of proteins associated with U-tAs using a high throughput, antibody-based method. A total of 111 proteins were identified that had a significant association between protein level in newborn cord blood and maternal U-tAs. Many of these proteins are regulated by tumor necrosis factor and are enriched in functionality related to immune/inflammatory response and cellular development/proliferation. Interindividual differences in proteomic response were observed in which 30 newborns were "activators," displaying a positive relationship between protein expression and maternal U-tAs. For 20 "repressor" newborns, a negative relationship between protein expression level and maternal U-tAs was observed. The activator/repressor status was significantly associated with maternal U-tAs and head circumference in newborn males. These results may provide a critical groundwork for understanding the diverse health effects associated with prenatal arsenic exposure and highlight interindividual responses to arsenic that likely influence differential susceptibility to adverse health outcomes.
生命早期接触无机砷（iAs）与婴儿、儿童和成人的健康不良影响有关，但这些影响的生物学机制仍研究不足。本研究旨在使用来自墨西哥戈麦斯·帕拉西奥的 50 名新生儿的脐带血样本，研究与产前 iAs 暴露相关的蛋白质组学变化。测定了母亲饮用水中的 iAs 水平（DW-iAs）和母亲尿液中 iAs 和 iAs 代谢物的总和（U-tAs）。分析了代表产前不同 iAs 暴露水平的脐带血样本（DW-iAs 范围从<1 到 236μg As/l），使用高通量、基于抗体的方法分析与 U-tAs 相关的蛋白质表达的改变。总共鉴定出 111 种蛋白质，它们的蛋白水平与新生儿脐带血中的 U-tAs 之间存在显著相关性。其中许多蛋白质受肿瘤坏死因子调节，并且富集在与免疫/炎症反应和细胞发育/增殖相关的功能中。在蛋白质组学反应中观察到个体间差异，其中 30 名新生儿为“激活剂”，表现出蛋白表达与母体 U-tAs 之间的正相关关系。对于 20 名“抑制剂”新生儿，观察到蛋白表达水平与母体 U-tAs 之间存在负相关关系。激活剂/抑制剂状态与母体 U-tAs 和新生儿男性头围显著相关。这些结果可能为理解与产前砷暴露相关的不同健康影响提供重要的基础，并强调个体对砷的反应，这可能影响对不良健康结果的易感性差异。
