Bonefeld-Jorgensen Eva C, Hjelmborg Philip S, Reinert Thayaline S, Andersen Birgitte S, Lesovoy Vladimir, Lindh Christian H, Hagmar Lars, Giwercman Aleksander, Erlandsen Mogens, Manicardi Gian-Carlo, Spanò Marcello, Toft Gunnar, Bonde Jens Peter
Unit of Cellular and Molecular Toxicology, Department of Environmental and Occupational Medicine, Institute of Public Health, Vennelyst Boulevard 6, Build, 1260, University of Aarhus, DK-8000 Aarhus, Denmark.
Environ Health. 2006 May 5;5:12. doi: 10.1186/1476-069X-5-12.
Human exposure to persistent organic pollutants (POPs) is ubiquitous and found in all individuals. Studies have documented endocrine disrupting effects and impact on reproduction. The aim of the present study was to compare the level of xenoestrogenic activity in serum of groups with varying POP exposure, and to evaluate correlations to the POP biomarkers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE).
The study included 358 men: Greenlandic Inuit's, Swedish fishermen, and Warsaw (Poland) and Kharkiv (Ukraine) inhabitants. Xenoestrogenicity of serum extracts alone (XER) and XER competitive (XERcomp) effect on 17beta-estradiol induced estrogen receptor (ER) transactivity were assessed in the hormone free, lipophilic serum fraction containing the POPs using the MVLN human breast cancer cell line.
No agonistic XER activity was exhibited for Inuit serum samples, while 12 - 24% of the European samples had detectable agonistic XER activity. On the contrary, 71% of Inuit serum samples antagonized XERcomp compared to 7 - 30 % in the other regions. XER and XERcomp were not or weakly correlated to the two POP markers. XER activity of Inuit samples was negatively associated to levels of CB-153 and p,p'-DDE. For the Warsaw group a positive and negative correlation between XER and p,p'-DDE and estradiol equivalence level and CB-153 levels was found.
No strong consistent association between xenoestrogenic net activity and the two POP markers was found. The results showed that the selected POP markers alone can not predict the integrated xenoestrogenic serum activity. Correlations to the POP markers were found at the extreme edge; the Inuit's and Warsaw study groups eliciting high frequency of samples with ER antagonistic and agonistic activity, respectively. We suggest that the variation in xenoestrogenic serum activity reflects differences in POP exposure mixture, genetic factors and/or life style factors.
人类接触持久性有机污染物（POPs）的情况普遍存在，在所有人中都能发现。研究已记录了其内分泌干扰作用以及对生殖的影响。本研究的目的是比较不同POP暴露水平组血清中的外源性雌激素活性水平，并评估与POP生物标志物2,2',4,4',5,5'-六氯联苯（CB - 153）和1,1 - 二氯 - 2,2 - 双（对氯苯基）乙烯（p,p'-DDE）的相关性。
该研究纳入了358名男性，包括格陵兰因纽特人、瑞典渔民以及华沙（波兰）和哈尔科夫（乌克兰）的居民。使用MVLN人乳腺癌细胞系，在含有POPs的无激素、亲脂性血清组分中，评估血清提取物单独的外源性雌激素活性（XER）以及XER竞争性（XERcomp）对17β - 雌二醇诱导的雌激素受体（ER）转录活性的影响。
因纽特人血清样本未表现出激动性XER活性，而12% - 24%的欧洲样本具有可检测到的激动性XER活性。相反，71%的因纽特人血清样本对XERcomp具有拮抗作用，而其他地区这一比例为7% - 30%。XER和XERcomp与两种POP标志物无相关性或相关性较弱。因纽特人样本的XER活性与CB - 153和p,p'-DDE水平呈负相关。对于华沙组，发现XER与p,p'-DDE以及雌二醇当量水平与CB - 153水平之间存在正相关和负相关。
未发现外源性雌激素净活性与两种POP标志物之间存在强的一致性关联。结果表明，仅所选的POP标志物无法预测血清中外源性雌激素的综合活性。在极端情况下发现了与POP标志物的相关性；因纽特人和华沙研究组分别出现具有ER拮抗和激动活性样本的高频情况。我们认为血清中外源性雌激素活性的差异反映了POP暴露混合物、遗传因素和/或生活方式因素的差异。
