Long Manhai, Andersen Birgitte S, Lindh Christian H, Hagmar Lars, Giwercman Aleksander, Manicardi Gian-Carlo, Bizzaro Davide, Spanò Marcello, Toft Gunnar, Pedersen Henning S, Zvyezday Valentyna, Bonde Jens Peter, Bonefeld-Jorgensen Eva C
Unit of Cellular & Molecular Toxicology, Department of Environmental and Occupational Medicine, Institute of Public Health, University of Aarhus, Vennelyst Boulevard 6, DK-8000 Aarhus C, Denmark.
Environ Health. 2006 May 25;5:14. doi: 10.1186/1476-069X-5-14.
Persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins/furans, polychlorinated biphenyls (PCBs) and organochlorine pesticides can cause a series of adverse effects on e.g. reproduction in animals and humans, many of which involve the aryl hydrocarbon receptor (AhR). The aim of the present study was to compare the integrated serum level of AhR mediated activity among European and Inuit populations, and evaluate whether the activity was associated to the selected POP markers, 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 338 males from Greenland (Inuit's), Sweden, Warsaw (Poland) and Kharkiv (Ukraine). The AhR transactivity of serum extracts alone (AhRag) and competitive AhR activity (AhRcomp) upon co-exposure with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were determined in the lipophilic serum fraction containing the POPs using the AhR mediated luciferase reporter Hepa1.12cR cell assay.
The European groups showed higher median level of AhR-TEQ (TCDD toxic equivalents) compared to the Inuit's, whereas higher incidence of Inuits sample further induced AhRcomp activity. Neither AhRag nor AhR-TEQ were correlated to CB-153 or p,p'-DDE for any of the study groups. Multiple regressions showed a significant heterogeneity of association between the CB-153 and the AhRcomp across the study groups, and accordingly a negative association between AhRcomp and CB-153 was found for the Kharkiv group.
No consistent correlation between AhR activities and two POP markers was found. Although the difference of AhRag between European and Inuit men could not be explained by CB-153 or p,p'-DDE levels alone, we believe that the variation of AhR serum activity reflects different pattern of POP exposure, genetics and/or life style factors.
多氯二苯并对二噁英/呋喃、多氯联苯（PCBs）和有机氯农药等持久性有机污染物（POPs）可对动物和人类的生殖等产生一系列不良影响，其中许多影响涉及芳烃受体（AhR）。本研究的目的是比较欧洲人和因纽特人群体中AhR介导活性的综合血清水平，并评估该活性是否与选定的POP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）相关。
该研究纳入了来自格陵兰（因纽特人）、瑞典、华沙（波兰）和哈尔科夫（乌克兰）的338名男性。使用AhR介导的荧光素酶报告基因Hepa1.12cR细胞试验，在含有POPs的亲脂性血清组分中测定单独血清提取物的AhR转录活性（AhRag）以及与2,3,7,8-四氯二苯并对二噁英（TCDD）共同暴露时的竞争性AhR活性（AhRcomp）。
与因纽特人相比，欧洲人群体的AhR-TEQ（TCDD毒性当量）中位数水平更高，而因纽特人样本中更高比例的样本进一步诱导了AhRcomp活性。对于任何研究组，AhRag和AhR-TEQ均与CB-153或p,p'-DDE无关。多元回归显示，在各研究组中，CB-153与AhRcomp之间存在显著的关联异质性，因此在哈尔科夫组中发现AhRcomp与CB-153之间存在负相关。
未发现AhR活性与两种POP标志物之间存在一致的相关性。尽管欧洲男性和因纽特男性之间AhRag的差异不能仅由CB-153或p,p'-DDE水平来解释，但我们认为AhR血清活性的变化反映了不同的POP暴露模式、遗传和/或生活方式因素。
