Prenatal exposure to polycyclic aromatic hydrocarbons, benzo[a]pyrene-DNA adducts, and genomic DNA methylation in cord blood.
Prenatal exposure to polycyclic aromatic hydrocarbons, benzo[a]pyrene-DNA adducts, and genomic DNA methylation in cord blood.
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DOI：
10.1289/ehp.1104056
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发表时间：
2012-05
影响因子：
10.4
通讯作者：
Perera FP
中科院分区：
文献类型：
--
作者：
Herbstman JB;Tang D;Zhu D;Qu L;Sjödin A;Li Z;Camann D;Perera FP
背景：多环芳烃（PAHs）是不完全燃烧过程中产生的致癌环境污染物。接触后和代谢过程中，PAH 可形成反应性环氧化物，可与 DNA 共价结合。这些 PAH-DNA 加合物是癌症风险的既定标记。 PAH 暴露与表观遗传改变有关，包括基因组胞嘧啶甲基化。特定基因的整体低甲基化和高甲基化都与人类癌症和其他疾病有关。实验证据表明 PAH-DNA 加合物的形成可能优先针对甲基化基因组区域。早期胚胎发育可能是 PAH 暴露特别敏感的时期，导致 PAH-DNA 加合物增加和 DNA 甲基化改变。目的：我们探讨产前接触 PAH 是否与脐带血中基因组 DNA 甲基化相关，以及甲基化水平是否与可检测到的 PAH-DNA 加合物的存在相关。方法：在纽约市不吸烟女性的一项纵向队列研究中，我们使用个人空气监测仪测量了怀孕期间的 PAH 暴露量，使用产前尿液代谢物（子集）评估了 PAH 内部剂量，并量化了 164 名参与者的苯并[a]芘-DNA 加合物和脐带血 DNA 中的基因组 DNA 甲基化。结果：产前 PAH 暴露与脐带白细胞中较低的整体甲基化水平相关 (p = 0.05)，但整体甲基化水平与脐带血中可检测到的加合物的存在呈正相关 (p = 0.01)。结论：这些观察结果表明，PAH 暴露足以改变我们研究人群的整体甲基化。可以测量位点特异性胞嘧啶甲基化和加合物形成的其他流行病学研究将提高我们理解体内这种复杂分子途径的能力。
Background: Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic environmental pollutants generated during incomplete combustion. After exposure and during metabolism, PAHs can form reactive epoxides that can covalently bind to DNA. These PAH–DNA adducts are established markers of cancer risk. PAH exposure has been associated with epigenetic alterations, including genomic cytosine methylation. Both global hypomethylation and hypermethylation of specific genes have been associated with cancer and other diseases in humans. Experimental evidence suggests that PAH–DNA adduct formation may preferentially target methylated genomic regions. Early embryonic development may be a particularly susceptible period for PAH exposure, resulting in both increased PAH–DNA adducts and altered DNA methylation. Objective: We explored whether prenatal exposure to PAHs is associated with genomic DNA methylation in cord blood and whether methylation levels are associated with the presence of detectable PAH–DNA adducts. Methods: In a longitudinal cohort study of nonsmoking women in New York City, we measured PAH exposure during pregnancy using personal air monitors, assessed PAH internal dose using prenatal urinary metabolites (in a subset), and quantified benzo[a]pyrene–DNA adducts and genomic DNA methylation in cord blood DNA among 164 participants. Results: Prenatal PAH exposure was associated with lower global methylation in umbilical cord white blood cells (p = 0.05), but global methylation levels were positively associated with the presence of detectable adducts in cord blood (p = 0.01). Conclusions: These observations suggest that PAH exposure was adequate to alter global methylation in our study population. Additional epidemiologic studies that can measure site-specific cytosine methylation and adduct formation will improve our ability to understand this complex molecular pathway in vivo.