The School of Pharmacy, University of London, Centre for Toxicology, London, UK.
Toxicol In Vitro. 2010 Sep;24(6):1757-63. doi: 10.1016/j.tiv.2009.12.017. Epub 2009 Dec 29.
2-Amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) is a heterocyclic amine which is found in food after cooking and which is a known mutagen. Reports from several laboratories have proposed that PhIP has estrogenic activity, which would classify PhIP as a xenoestrogen with human exposure via food. We tested PhIP in two cell-based assays for estrogenicity, both based on human cell lines but utilising different outcome measures: ERLUX (reporter-gene activation) and ESCREEN (cell proliferation). PhIP was inactive in both assays at concentrations spanning the picomolar to micromolar range. To eliminate supplier differences as an explanation for the disparity between these results and positive findings in the literature, we purchased PhIP from three suppliers and found no detectable estrogenic activity in any batch. (1)H NMR spectroscopy confirmed the chemical identity of the tested stock solutions. Correct assay performance was confirmed by including positive and vehicle controls on every assay plate, and by demonstrating the expected responses to a panel of known estrogens (estradiol, bisphenol A, and genistein). Our results differ from those in the literature and, whilst the exact reason for this is unknown, we discuss possible explanations of the disparity. Our results provide no in vitro evidence for the classification of PhIP as an estrogen.
2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP）是一种杂环胺，在烹饪后存在于食物中，是一种已知的致突变物。几个实验室的报告表明，PhIP 具有雌激素活性，这将使其归类为具有人类暴露于食物的外源性雌激素。我们在两种基于细胞的雌激素活性检测中测试了 PhIP，这两种检测均基于人细胞系，但采用了不同的结果测量方法：ERLUX（报告基因激活）和 ESCREEN（细胞增殖）。在 picomolar 到 micromolar 浓度范围内，PhIP 在这两种检测中均无活性。为了排除供应商差异是导致这些结果与文献中阳性结果不一致的原因，我们从三个供应商处购买了 PhIP，在任何一批产品中均未检测到可检测的雌激素活性。（1）H NMR 光谱学确认了所测试的储备溶液的化学同一性。通过在每个检测板上包含阳性和载体对照物，并通过证明对一系列已知雌激素（雌二醇、双酚 A 和染料木黄酮）的预期反应，证实了正确的检测性能。我们的结果与文献中的结果不同，虽然确切原因尚不清楚，但我们讨论了差异的可能解释。我们的结果没有提供 PhIP 作为雌激素分类的体外证据。
