Assessment of total effective xenoestrogen burden in adipose tissue and identification of chemicals responsible for the combined estrogenic effect
Assessment of total effective xenoestrogen burden in adipose tissue and identification of chemicals responsible for the combined estrogenic effect
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DOI：
10.1007/s00216-004-2558-5
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发表时间：
2004-05-01
影响因子：
4.3
通讯作者：
Olea, N
中科院分区：
文献类型：
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作者：
Fernández, MF;Rivas, A;Olea, N
内分泌干扰的流行病学研究需要有检测系统来筛选雌激素性和人类接触的适当生物标志物。我们通过开发和标准化一种方法来评估人体脂肪组织中总的雌激素外源性物质负荷来解决这些问题。在这项研究中，这是以前的工作的延续，我们已经改进了大量的组织样本的广泛分馏的协议，以调查生物积累的异种雌激素的候选人的雌激素，并评估其组合的雌激素效应。这是通过将外源性雌激素与内源性激素进行广泛的HPLC分离，然后在E-Screen试验中检测单个组分的雌激素活性来实现的。有机氯农药，多氯联苯和卤代双酚和烷基酚收集在最亲脂的馏分，其次是孕激素，雄激素和雌二醇酯，然后由甾体雌激素;植物和真菌雌激素收集的运行结束。这些结果通过详尽的化学分析得到证实。在458份人体脂肪组织样本中，含有有机卤代异种雌激素的合并部分中75%的样本（平均值515.3 pM Eeq/g脂质;范围0-14.5 nM）和天然雌激素洗脱的合并部分中82%的样本（平均值696.6 pM Eeq/g脂质;范围0-12.9 nM）的总有效异种雌激素负荷为阳性。有机氯农药成为候选化学品的雌激素的第一个汇集部分，因为滴滴涕和衍生物存在于98.3%的样品。然而，没有发现任何单一化学品的浓度和在生物测定中确定的雌激素活性之间的相关性。这种不一致性可能有几个原因：（i）E-Screen生物测定中描述的雌激素效应是几种有机卤素化合物联合作用的结果，或（ii）增殖效应是由于未测量的其他化学物质。由于相加、协同或拮抗机制可能导致在合并组分中观察到的最终效应，因此，本工作中提出的方法更适合流行病学研究中的接触评估，而不是确定人体样本中的单个化学品。
Test systems to screen for estrogenicity and appropriate biomarkers of human exposure are required for epidemiological studies of endocrine disruption. We addressed these issues by developing and standardising a method to assess the total estrogenic xenobiotic burden in human adipose tissue. In this study, which is the continuation of a previous work, we have improved the protocol for extensive fractionation of a higher number of tissue samples in order to investigate bioaccumulated xenoestrogens that are candidates for estrogenicity and to assess their combined estrogenic effect. This was achieved by extensive HPLC separation of xenoestrogens from endogenous hormones followed by testing of individual fractions in the E-Screen test for estrogenicity. Organochlorine pesticides, PCBs and halogenated bisphenols and alkylphenols were collected in the most lipophilic fractions, followed by progestins, androgens and estradiol esters, and then by steroidal estrogens; phyto- and myco-estrogens were collected around the end of the run. These results were confirmed by exhaustive chemical analysis. In 458 human adipose tissue samples, the total effective xenoestrogen burden was positive in 75% of samples in the pooled fraction that contained organohalogenated xenoestrogens (mean 515.3 pM Eeq/g lipid; range 0-14.5 nM) and in 82% of samples in the pooled fraction where natural estrogens eluted (mean 696.6 pM Eeq/g lipid; range 0-12.9 nM). Organochlorine pesticides emerged as candidate chemicals for the estrogenicity of the first pooled fraction, because DDT and derivatives were present in 98.3% of the samples. However, no correlation was found between the concentration of any single chemical and the estrogenicity determined in the bioassay. There may be several reasons for this lack of concordance: (i) the estrogenic effects depicted in the E-Screen bioassay are a consequence of the combined effect of several organohalogens or (ii) the proliferative effect is due to other chemicals not measured. Because additive, synergistic or antagonistic mechanisms may account for the final effect observed in the pooled fractions, the approach proposed in this work is more appropriate for exposure assessment in epidemiological studies than the determination of individual chemicals in human samples.