Similarities in the Endocrine-Disrupting Potencies of Indoor Dust and Flame Retardants by Using Human Osteosarcoma (U2OS) Cell-Based Reporter Gene Assays
Similarities in the Endocrine-Disrupting Potencies of Indoor Dust and Flame Retardants by Using Human Osteosarcoma (U2OS) Cell-Based Reporter Gene Assays
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DOI：
10.1021/es304691a
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发表时间：
2013-03-19
影响因子：
11.4
通讯作者：
Taldgami, Hidetaka
中科院分区：
文献类型：
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作者：
Suzuki, Go;Nguyen Minh Tue;Taldgami, Hidetaka
室内粉尘是多种污染物的汇，包括阻燃剂（FR）、增塑剂及其污染物和降解产物。这些污染物可以从电视机和电脑等家用物品迁移到室内灰尘中。为了揭示室内灰尘中的高优先级终点和污染物候选者，使用基于人骨肉瘤（U2OS）细胞系的CALUX报告基因测定，我们评估并表征了从日本（n = 8），美国（n = 21），越南（n = 10），菲律宾（n = 17），和印度尼西亚（n = 10）和23个选定的FR。所用CALUX报告基因测定对与人雄激素受体（AR）、雌激素受体α（ER α）、孕酮受体（PR）、糖皮质激素受体（GR）和过氧化物酶体增殖物激活受体γ 2（PPAR γ 2）相互作用的化合物具有特异性。室内灰尘提取物对ER α、GR和PPAR γ 2具有激动作用，对AR、PR、GB具有拮抗作用，和过氧化物酶体增殖物激活受体γ 2。相比之下，大多数FR仅对ER α和PPAR γ 2具有激动作用，并且一些FR表现出对所有测试的核受体的受体特异性拮抗作用。分层聚类清楚地表明，激动的ER α和拮抗的AR和PR是常见的，经常检测到的室内灰尘和测试的FR的终点。鉴于我们先前关于室内灰尘中阻燃剂浓度的研究结果以及我们目前的研究结果，这些影响的潜在促成因素不仅包括受国际管制的溴化阻燃剂，还包括一些含磷阻燃剂等替代品。在室内污染的背景下，FR的高频效应，如ER α的激动作用和AR和PR的拮抗作用是进一步研究的候选高优先级终点。
Indoor dust is a sink for many kinds of pollutants, including flame retardants (FRs), plasticizers, and their contaminants and degradation products. These pollutants can be migrated to indoor dust from household items such as televisions and computers. To reveal high-priority end points of and contaminant candidates in indoor dust, using CALUX reporter gene assays based on human osteosarcoma (U2OS) cell lines, we evaluated and characterized the endocrine-disrupting potencies of crude extracts of indoor dust collected from Japan (n = 8), the United States (n = 21), Vietnam (n = 10), the Philippines (n = 17), and Indonesia (n = 10) and for 23 selected FRs. The CALUX reporter gene assays used were specific for compounds interacting with the human androgen receptor (AR), estrogen receptor alpha (ER alpha), progesterone receptor (PR), glucocorticoid receptor (GR), and peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2). Indoor dust extracts were agonistic to ER alpha, GR, and PPAR gamma 2 and antagonistic against AR, PR, GB., and PPAR gamma 2. In comparison, a majority of FRs was agonistic to ER alpha and PPAR gamma 2 only, and some FRs demonstrated receptor-specific antagonism against all tested nuclear receptors. Hierarchical clustering clearly indicated that agonism of ER alpha and antagonism of AR and PR were common, frequently detected end points for indoor dust and tested FRs. Given our previous results regarding the concentrations of FRs in indoor dust and in light of our current results, candidate contributors to these effects include not only internationally controlled brominated FRs but also alternatives such as some phosphorus-containing FRs. In the context of indoor pollution, high-frequency effects of FRs such as agonism of ER alpha and antagonism of AR and PR are candidate high-priority end points for further investigation.