Low-dose treatment with polybrominated diphenyl ethers (PBDEs) induce altered characteristics in MCF-7 cells
Low-dose treatment with polybrominated diphenyl ethers (PBDEs) induce altered characteristics in MCF-7 cells
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DOI：
10.1093/mutage/gel038
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发表时间：
2006-09-01
期刊：
影响因子：
2.7
通讯作者：
Martin, Francis L.
中科院分区：
文献类型：
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作者：
Barber, Jonathan L.;Walsh, Michael J.;Martin, Francis L.
多溴联苯醚(PBDEs)是一种疏水、持久的添加剂阻燃剂，它们似乎会转移到环境隔间中，在那里它们会生物积累，即在人类生物群中。我们检测了低剂量多溴二苯醚(47、99、153、183或209)在MCF-7细胞中的微核形成活性及其对生长的调节能力、细胞生化[通过红外(IR)显微光谱]、克隆存活或细胞色素P450同工酶(CYP1A1、CYP1A2和CYP1B1)、细胞周期蛋白依赖的激酶抑制因子1A[CDKN1A(P21(WAF1/CIP1))]、B细胞白血病/淋巴瘤-2(BCL-2)和细胞色素P450同工酶(Bax)的定量表达。在10(-12)到10(-9)M多溴二苯醚浓度处理后，观察到微核形成的增加，尽管每个试验剂浓度的不到四分之一被分配出培养基并进入孵育细胞。然而，低剂量治疗水平仍然在2003年收集的英国血清样本中报告的浓度范围内。在10(-12)~10(-9)M PBDE处理后，克隆存活率和基因表达没有改变，但生长动力学显著提高(P<；0.05)。红外细胞光谱的显著变化与处理有关，主成分分析后绘制的聚类图突出了这些变化。这种体外效应是否指向多溴二苯醚在体内启动和驱动靶细胞改变的潜在能力，现在需要解决。
Polybrominated diphenyl ethers (PBDEs) are hydrophobic and persistent additive flame retardants that seemingly transfer into environmental compartments where they bioaccumulate i.e. in human biota. We examined the micronucleus-forming activities of low-dose PBDEs (congeners 47, 99, 153, 183 or 209) in MCF-7 cells along with their ability to modulate growth, cell biochemistry [by infrared (IR) microspectroscopy], clonogenic survival or quantitative expression of cytochrome P450 isoenzymes (CYP1A1, CYP1A2 and CYP1B1), cyclin-dependent kinase inhibitor 1A [CDKN1A (P21(WAF1/CIP1))], B-cell leukaemia/lymphoma-2 (BCL-2) and Bcl-2-associated X (BAX). Elevations in micronucleus formation were observed following treatment with 10(-12) to 10(-9) M PBDE concentrations despite the fact that less than one-fourth of the concentration of each test agent administered partitioned out of the media and into the incubating cells. However, low-dose treatment levels remained within the range of reported concentrations measured in UK serum samples collected in 2003. Clonogenic survival and gene expression was unaltered following 10(-12) to 10(-9) M PBDE treatment but significant (P < 0.05) elevations in growth kinetics were observed. Significant alterations in IR cell spectra were associated with treatments, and plotted clusters following principal component analysis highlighted these changes. Whether such in vitro effects point to an underlying ability of PBDEs to initiate and drive target-cell alterations in vivo now needs to be addressed.