Barber Jonathan L, Walsh Michael J, Hewitt Rebecca, Jones Kevin C, Martin Francis L
Department of Environmental Science, Lancaster University Lancaster LA1 4YQ, UK.
Mutagenesis. 2006 Sep;21(5):351-60. doi: 10.1093/mutage/gel038. Epub 2006 Sep 16.
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.
多溴二苯醚(PBDEs)是疏水性且持久的添加型阻燃剂,似乎会转移到环境隔室中并在其中生物累积,即在人类生物群中。我们研究了低剂量多溴二苯醚(同系物47、99、153、183或209)在MCF-7细胞中的微核形成活性,以及它们调节生长、细胞生物化学(通过红外光谱)、克隆形成存活率或细胞色素P450同工酶(CYP1A1、CYP1A2和CYP1B1)、细胞周期蛋白依赖性激酶抑制剂1A [CDKN1A (P21(WAF1/CIP1))]、B细胞白血病/淋巴瘤-2(BCL-2)和Bcl-2相关X蛋白(BAX)定量表达的能力。在用10⁻¹²至10⁻⁹ M的多溴二苯醚浓度处理后,观察到微核形成增加,尽管所施用的每种测试剂浓度中不到四分之一从培养基中分配到培养的细胞中。然而,低剂量处理水平仍在2003年采集的英国血清样本中测得的报告浓度范围内。在用10⁻¹²至10⁻⁹ M的多溴二苯醚处理后,克隆形成存活率和基因表达未改变,但观察到生长动力学有显著(P < 0.05)升高。红外细胞光谱的显著变化与处理有关,主成分分析后的绘制聚类突出了这些变化。现在需要解决的是,这种体外效应是否表明多溴二苯醚在体内引发和驱动靶细胞改变的潜在能力。