儿童体内多环芳烃暴露水平与DNA损伤和肺功能间的关系

Polycylic aromatic hydrocarbons (PAHs) are the carcinogenic compounds with high toxicity. Even the long time exposure to low level will lead to DNA damage and chronic respiratory disease, especially for children due to their sensitivity. As Guangzhou ranked 5 in 14 cities with high environmental PAHs environment in China, especially in winter,the local residents may be exposure to PAHs with high environmental risk. Our objectives of this study is to investigate the dose -effect related relationship between carcinogenic target compounds and their DNA damage, as well as PAH exposure effects on lung function for children living in Guangzhou. Children who has chronic respiratory disease (such as bronchial asthma,chronic obstructive pulmoary disease, pneumonia et al) with the age between 6-11 years old in Guangzhou are recruited，and the healthy children in Conghua were recruited as the control group. 12 urinary hydroxylated PAH metabolites are selected as the biomarkers to assess the short-term exposure levels to PAHs. The profile levels and characterization of PAHs exposure will be fully discussed and the environment risk of PAHs exposure will be assessed by using urinary PAHs exposure. 8-hydoxy-2'-deoxyguanosine (8-OHdG) in urine and specific Benzo(a)pyrene [B(a)P] diolepoxide (BPDE)-adduct in peripheral blood are used respectively as the short and long-term biomarkers to evaluate the effects of PAHs on DNA damage, as well as the environmental risks. The method of 32p postlabelling coupled with liquid chromatography to quantify the BPDE-DNA adduct in blood will be developed and standardized. Chromatographic method pretreated with multiple clean-up procedures may lower the detection limit of BPDE-DNA adduct. The dose-response associations between PAHs exposure and DNA damage and the most sensitive biomarker to assess the PAHs exposure will be investigated. Lung function and serum interleukin-8 (IL-8) are used as the early biomarkers o effect to assess the PAH pollution on respiration system. Furthermore, based on the suitable and sensitive variables, factor analysis will be used to set up a quantitation model to discript the association beween urinary PAHs exposure and DNA damage, lung function. In one word, the study is scientifically significant and a combination of analytical chemistry and toxicology in the employment of environment science. The combination and employment of epidemiology, statistics, analytical chmistry and mathematical model in environment science will give a profile assessments of the PAHs exposure on children's respiration health hazards and broaden the research depth.

多环芳烃（PAHs）是一类具有"三致"效果的高毒性有机化合物，长期低浓度环境暴露，对细胞和DNA造成损伤,从而引起各种严重的慢性呼吸道疾病。研究以广州市患有各种慢性呼吸道疾病的儿童为对象，以尿中12种单羟基多环芳烃作为PAHs短期暴露的标志物,测定儿童体内PAH水平，分析其特点并评估其环境风险；以尿中8-羟基脱氧鸟苷和血中特异性的7，8-二醇-9，10-环氧苯并芘（BPDE）-DNA加合物为标志物评价PAHs长期暴露对DNA的损伤；用肺功能和血清中白细胞介素-作为一个早期效应指标评价PAHs污染暴露对呼吸系统的不良影响。找寻和鉴定PAHs暴露对肺功能和呼吸道系统损伤最灵敏和适用的生物标志物。并结合大气资料和生活饮食习惯，从尿中PAHs代谢产物和DNA加合物角度综合评价PAHs典型城市环境污染对儿童健康的潜在危害，建立数学模型对PAHs内暴露与肺功能和DNA损伤进行量化描述,具有明显创新性。

多环芳烃(PAHs)和苯系物（BTEX）是大气中具有三致效应的污染物，长时间暴露于PAHs和BTEX，易引起呼吸道疾病，甚至肺癌。本研究以对PAHs和BTEX易感的人群-来自广州的患有呼吸道疾病的儿童以及长时间生活在北方某燃煤区的普通儿童为研究对象，以尿中10 种单羟基多环芳烃和4种BTEX代谢产物作为PAHs和BTEX短期暴露的标志物，测定儿童体内PAH/BTEX水平，分析其特点并评估其环境风险；以尿中8-羟基脱氧鸟苷和血中特异性的 7，8-二醇-9，10-环氧苯并芘（BPDE）-DNA 加合物为标志物评价PAHs长期暴露对DNA的损伤；用肺功能和血清中白细胞介素-作为一个早期效应指标评价PAHs和BTEX污染暴露对呼吸系统的不良影响。通过统计分析工具分析PAHs/BTEX 暴露对肺功能和呼吸道系统损伤最灵敏和适用的生物标志物及PAHs 内暴露与肺功能和 DNA 损伤之间的剂量-效应关系。结果显示，中国南方非燃煤区（广州）以及北方某燃煤区儿童尿中PAHs和BTEX暴露水平均高于欧美国家同龄儿童水平的2-8倍，显示可能具有负担了较高的环境风险，但每日PAHs摄入量仍低于美国EPA的安全值；PAHs和BTEX暴露引起体内DNA氧化损伤和炎症因子水平的升高，且呈剂量和效应关系，一个百分比的PAHs暴露导致0.33%的DNA氧化损伤，1个百分比的BTEX产生0.02%的8-OHdG；广州儿童体内PAHs和BTEX暴露与肺功能无关，但燃煤区儿童肺功能中的第一秒时间用力呼出气体容量（FEV1）和最大呼气中段流速(FEF25%)与PAHs暴露显著相关；尿中1-羟基萘、3-羟基菲、4-羟基菲以及1-羟基芘含量的升高导致FEV1和 FEF25%显著下降；患呼吸道疾病儿童血中的BPDE-DNA加合物水平明显高于健康儿童，且与总的DNA损伤和IL-8显著相关，且导致肺功能的下降，但尚未达到显著性水平。这说明尿中PAHs，特别是1-羟基芘是一个很好的生物标志物，可以指示大气污染较重地区普通人群的PAHs暴露及肺功能的损伤，而对于清洁地区普通人群来讲BPDE-DNA加合物既是一个很好的PAHs暴露的指示物，也是一个指示健康风险的标志物。