Villeneuve D L, Khim J S, Kannan K, Giesy J P
Department of Zoology, National Food Safety and Toxicology Center, Institute for Environmental Toxicology, Michigan State University, East Lansing, Michigan 48824, USA.
Environ Toxicol. 2002;17(2):128-37. doi: 10.1002/tox.10041.
The dioxinlike and estrogenic relative potencies (REPs) of 16 priority polycyclic aromatic hydrocarbons (PAHs), seven methylated PAHs, and two hydroxylated PAHs were examined using three in vitro cell bioassays. An in vitro ethoxyresorufin-O-deethylase assay with PLHC-1 fish hepatoma cells and in vitro luciferase assay with H4IIE-luc recombinant rat hepatoma cells were used to evaluate dioxinlike potency. An in vitro luciferase assay with MVLN, recombinant human breast carcinoma cells, was used to evaluate estrogenic potency. Seven of the 16 priority PAHs tested induced significant dioxinlike responses. Excluding outliers with large ranges of uncertainty, the dioxinlike REPs for the PAHs ranged from 10(-6) to 10(-3). This is similar to the REPs reported for other xenobiotics of concern including polychlorinated naphthalenes (PCNs) and some polychlorinated biphenyls (PCBs). In general, REP estimates generated in this study were similar to those reported previously. However, a comparison of the estimates of total 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents derived using assay-specific REPs with REPs reported in other studies indicated that the use of nonspecific REPs could lead to significant error in mass-balance (potency-balance) analyses. A 10-h acid treatment completely destroyed the dioxinlike activity of a PAH mixture. Among the compounds tested, only benzo[a]anthracene and dibenz[a,h]anthracene induced significant responses in the MVLN bioassay. Relative estrogenic potencies were estimated to be approximately 10(-7). Overall, this research contributes to the growing consensus regarding the dioxinlike potency of priority PAHs and PAH derivatives and provides some additional evidence about potentially estrogenic PAHs.
使用三种体外细胞生物测定法检测了16种优先多环芳烃(PAHs)、7种甲基化PAHs和2种羟基化PAHs的二噁英样和雌激素相对效力(REPs)。采用PLHC-1鱼肝癌细胞的体外乙氧基异吩噁唑酮-O-脱乙基酶测定法和H4IIE-luc重组大鼠肝癌细胞的体外荧光素酶测定法来评估二噁英样效力。采用MVLN重组人乳腺癌细胞的体外荧光素酶测定法来评估雌激素效力。所检测的16种优先PAHs中有7种诱导了显著的二噁英样反应。排除具有较大不确定性范围的异常值后,PAHs的二噁英样REPs范围为10^(-6)至10^(-3)。这与报道的其他相关外源性物质(包括多氯萘(PCNs)和一些多氯联苯(PCBs))的REPs相似。总体而言,本研究得出的REP估计值与先前报道的相似。然而,将使用特定测定法的REPs得出的总2,3,7,8-四氯二苯并-p-二噁英当量估计值与其他研究报道的REPs进行比较表明,使用非特异性REPs可能会在质量平衡(效力平衡)分析中导致显著误差。10小时的酸处理完全破坏了PAH混合物的二噁英样活性。在所测试的化合物中,只有苯并[a]蒽和二苯并[a,h]蒽在MVLN生物测定中诱导了显著反应。相对雌激素效力估计约为10^(-7)。总体而言,本研究有助于就优先PAHs和PAH衍生物的二噁英样效力形成越来越多的共识,并提供了一些关于潜在雌激素性PAHs的额外证据。