VITO Health, Flemish Institute for Technological Research (VITO), Mol, Belgium.
Provincial Institute of Hygiene (PIH), Antwerp, Belgium.
Environ Res. 2020 Nov;190:110002. doi: 10.1016/j.envres.2020.110002. Epub 2020 Aug 1.
The Flemish Environment and Health Studies (FLEHS) are human biomonitoring surveys running in Flanders since 1999. Additionally to biomarkers of exposure, markers of genotoxicity and oxidative stress have been measured, including the alkaline comet and micronucleus assay in peripheral whole blood cells, and urinary concentrations of 8-oxo-2'-deoxyguanosine (8-oxodG).
Exposure-effect associations were explored in a pooled dataset of nine different cross-sectional FLEHS surveys. Data of adolescents collected in a time frame of about 20 years (1999-2018) were compiled. The aim of the study was to examine whether increased variation in exposure, lifestyle and environmental factors would lead to more powerful and robust exposure-effect associations.
MATERIALS & METHODS: The biomarkers were measured in 2283 adolescents in the age range of 14-18 years. Exposure to polycyclic aromatic hydrocarbons [1-hydroxypyrene (1-OHP)], benzene (tt'-muconic acid), metals (arsenic, cadmium, copper, nickel, thallium, lead, chromium), persistent organochlorines and phthalates were assessed in blood or urine. Furthermore, outdoor air levels of particulate matter (PM and PM) at the residences of the youngsters were calculated. Pooled statistical analysis was done using mixed models. Study-specific differences in the genotoxicity markers and in the strength/direction of the association were accounted for. This was done by incorporating the random factor 'study' and a random study slope (if possible). The exposure markers were centered around the study-specific mean in order to correct for protocol changes over time.
A significant association was observed for the urinary oxidative stress marker 8-oxodG, which was positively associated with 1-OHP (5% increase for doubling of 1-OHP levels, p = 0.001), and with urinary copper (26% increase for doubling of copper levels, p = 0.001), a metal involved in the Fenton reaction in biological systems. 8-oxodG was also associated with the sum of the metabolites of the phthalate di(2-ethylhexyl) phthalate (DEHP) (3% increase for doubling of the DEHP levels, p = 0.02). For those associations, data pooling increased the statistical power. However, some of the associations in the individual surveys, were not confirmed in the pooled analysis (such as comet assay and 8-oxodG vs. atmospheric PM; and 8-oxodG vs. urinary nickel). This may be due to inconsistencies in exposure-effect relations and/or variations in the pollutant mix over time and regions.
Pooled analysis including a large population of 2283 Flemish adolescents showed that 8-oxodG, a marker of oxidative DNA damage is a valuable marker to assess impact of daily life pollutants, such as PAHs, Cu and the phthalate DEHP.
自 1999 年以来，佛兰德环境与健康研究（FLEHS）一直在进行人体生物监测调查。除了接触生物标志物外，还测量了遗传毒性和氧化应激标志物，包括外周全血细胞的碱性彗星和微核试验，以及尿液中 8-氧-2'-脱氧鸟苷（8-oxodG）的浓度。
在九个不同的 FLEHS 横断面研究的汇总数据集中探索暴露-效应关系。大约 20 年（1999-2018 年）的青少年数据被汇编。该研究的目的是检查接触、生活方式和环境因素的变化是否会导致更强大和更稳健的暴露-效应关联。
在年龄在 14-18 岁的 2283 名青少年中测量了这些生物标志物。通过血液或尿液评估多环芳烃[1-羟基芘（1-OHP）]、苯（tt'-粘康酸）、金属（砷、镉、铜、镍、铊、铅、铬）、持久性有机氯农药和邻苯二甲酸酯的暴露情况。此外，还计算了青少年居住地的大气颗粒物（PM 和 PM）的水平。使用混合模型进行汇总统计分析。考虑了遗传毒性标志物的研究特异性差异以及关联的强度/方向。这是通过纳入随机因子“研究”和随机研究斜率（如果可能）来实现的。为了纠正随时间推移的方案变化，将暴露标志物中心化在研究特异性平均值周围。
观察到尿液氧化应激标志物 8-oxodG 与 1-OHP 之间存在显著关联（1-OHP 水平加倍时增加 5%，p=0.001），与尿液铜之间存在正相关（铜水平加倍时增加 26%，p=0.001），铜是生物系统中芬顿反应的金属。8-oxodG 还与邻苯二甲酸二（2-乙基己基）酯（DEHP）代谢物的总和相关（DEHP 水平加倍时增加 3%，p=0.02）。对于这些关联，数据汇总增加了统计功效。然而，在汇总分析中，一些个体研究中的关联没有得到证实（例如彗星试验和 8-oxodG 与大气 PM；以及 8-oxodG 与尿镍）。这可能是由于暴露-效应关系的不一致性和/或随时间和地区的污染物组合的变化。
包括 2283 名佛兰德青少年的大型人群的汇总分析表明，8-oxodG，一种氧化 DNA 损伤的标志物，是评估日常生活污染物（如多环芳烃、Cu 和邻苯二甲酸二乙酯 DEHP）影响的有价值的标志物。
