中国人群中脐血和脐带组织中多环芳烃-DNA加合物水平与胎儿神经管缺陷风险
Levels of PAH-DNA adducts in cord blood and cord tissue and the risk of fetal neural tube defects in a Chinese population.
作者信息
Yi Deqing, Yuan Yue, Jin Lei, Zhou Guodong, Zhu Huiping, Finnell Richard H, Ren Aiguo
机构信息
Institute of Reproductive and Child Health and Ministry of Health Key Laboratory of Reproductive Health, Peking University, Beijing 100191, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.
Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA.
出版信息
Neurotoxicology. 2015 Jan;46:73-8. doi: 10.1016/j.neuro.2014.12.003. Epub 2014 Dec 15.
INTRODUCTION
Maternal exposure to polycyclic aromatic hydrocarbons (PAHs) has been shown to be associated with an elevated risk for neural tube defects (NTDs). In the human body, PAHs are bioactivated and the resultant reactive epoxides can covalently bind to DNA to form PAH-DNA adducts, which may, in turn, cause transcription errors, changes in gene expression or altered patterns of apoptosis. During critical developmental phases, these changes can result in abnormal morphogenesis.
OBJECTIVES
We aimed to examine the relationship between the levels of PAH-DNA adducts in cord blood and cord tissue and the risk of NTDs.
METHODS
From 2010 to 2012, 60 NTD cases and 60 healthy controls were recruited from a population-based birth defects surveillance system in five counties of Shanxi Province in Northern China, where the emission of PAHs remains one of the highest in the country and PAHs exposure is highly prevalent. PAH-DNA adducts in cord blood of 15 NTD cases and 15 control infants, and in cord tissue of 60 NTD cases and 60 control infants were measured using the (32)P-postlabeling method.
RESULTS
PAH-DNA adduct levels in cord blood tend to be higher in the NTD group (28.5 per 10(8) nucleotides) compared with controls (19.7 per 10(8) nucleotides), although the difference was not statistically significant (P=0.377). PAH-DNA adducts in cord tissue were significantly higher in the NTD group (24.6 per 10(6) nucleotides) than in the control group (15.3 per 10(6) nucleotides), P=0.010. A positive dose-response relationship was found between levels of PAH-DNA adducts in cord tissue and the risk of NTDs (P=0.009). When the lowest tertile was used as the referent and potential confounding factors were adjusted for, a 1.03-fold (95% CI, 0.37-2.89) and 2.96-fold (95% CI, 1.16-7.58) increase in the risk of NTDs was observed for fetuses whose cord tissue PAH-DNA adduct levels were in the second and highest tertile, respectively.
CONCLUSIONS
High levels of PAH-DNA adducts in fetal tissues were associated with increased risks of NTDs.
引言
已表明孕妇接触多环芳烃（PAHs）与神经管缺陷（NTDs）风险升高有关。在人体中，多环芳烃会发生生物活化，生成的反应性环氧化物可与DNA共价结合形成多环芳烃 - DNA加合物，进而可能导致转录错误、基因表达变化或凋亡模式改变。在关键发育阶段，这些变化可能导致形态发生异常。
目的
我们旨在研究脐血和脐带组织中多环芳烃 - DNA加合物水平与神经管缺陷风险之间的关系。
方法
2010年至2012年，从中国北方山西省五个县的基于人群的出生缺陷监测系统中招募了60例神经管缺陷病例和60例健康对照。在中国，山西省这五个县的多环芳烃排放量居全国前列，多环芳烃暴露非常普遍。使用（32）P后标记法测量了15例神经管缺陷病例和15例对照婴儿的脐血以及60例神经管缺陷病例和60例对照婴儿的脐带组织中的多环芳烃 - DNA加合物。
结果
神经管缺陷组脐血中的多环芳烃 - DNA加合物水平（每10^8个核苷酸28.5个）虽高于对照组（每10^8个核苷酸19.7个），但差异无统计学意义（P = 0.377）。神经管缺陷组脐带组织中的多环芳烃 - DNA加合物（每10^6个核苷酸24.6个）显著高于对照组（每10^6个核苷酸15.3个），P = 0.010。在脐带组织中多环芳烃 - DNA加合物水平与神经管缺陷风险之间发现了正剂量反应关系（P = 0.009）。当以最低三分位数作为参照并对潜在混杂因素进行校正后，脐带组织多环芳烃 - DNA加合物水平处于第二和最高三分位数的胎儿，其神经管缺陷风险分别增加了1.03倍（95%CI，0.37 - 2.89）和2.96倍（95%CI，1.16 - 7.58）。
结论
胎儿组织中高水平的多环芳烃 - DNA加合物与神经管缺陷风险增加有关。
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