Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, 3508 TD Utrecht, The Netherlands.
Environ Toxicol Chem. 2010 Jul;29(7):1529-36. doi: 10.1002/etc.187.
The present study is the second in a series aiming at a systematic inventory of specific toxic effects of oils. By employing a recombinant yeast stably transfected with human estrogen receptor-alpha (ERalpha) or -beta (ERbeta) or androgen receptor (AR) and expressing yeast enhanced green fluorescent protein, the (anti-)estrogenicity and (anti-)androgenicity of 11 crude oils and refined products were studied. None of the oils tested had significant estrogenic effects in the ERalpha assay or androgenic effects in the AR assay. However, all oils were capable of inducing estrogenic responses in the ERbeta assay, with several responses being above even the maximal response of the standard 17beta-estradiol (E2). Based on the lowest effect concentrations, the potencies of oils in all the assays were between four and seven orders of magnitude lower than those of the standards E2 or testosterone (T). The potencies of the actual individual petrochemical agonists may, however, be relatively high, considering the complex composition of oils. Additive effects, antagonistic effects, and a synergistic effect were measured in the assays upon coexposure to a fixed concentration of standard (E2 or T) and increasing concentrations of oils. To investigate whether the observed effects were receptor-mediated, coexposures to the synthetic inhibitors ICI 182,780 (ERbeta assay) or flutamide (AR assay), a fixed concentration of standard, and various concentrations of oils were performed. The results suggested that the androgenic effects were receptor mediated, whereas the estrogenic effects may be only partially mediated via the receptor. The present study indicates that oils contain compounds with possible endocrine-disrupting potential, some of them acting via the hormone receptors.
本研究是旨在对油类的特定毒性作用进行系统调查的系列研究中的第二项。通过使用稳定转染人雌激素受体-α（ERα）或-β（ERβ）或雄激素受体（AR）的重组酵母和表达酵母增强型绿色荧光蛋白，研究了 11 种原油和精炼产品的（抗）雌激素和（抗）雄激素作用。在 ERα 测定中，没有一种油具有显著的雌激素作用，在 AR 测定中也没有雄激素作用。然而，所有油都能够在 ERβ 测定中诱导雌激素反应，其中一些反应甚至超过了标准 17β-雌二醇（E2）的最大反应。基于最低效应浓度，所有油在所有测定中的效价均比标准 E2 或睾酮（T）的效价低四到七个数量级。然而，考虑到油的复杂组成，实际的个别石油类激动剂的效价可能相对较高。在固定浓度的标准（E2 或 T）和增加浓度的油共暴露的测定中，测量了加性效应、拮抗效应和协同效应。为了研究观察到的效应是否是受体介导的，在固定浓度的标准和各种浓度的油共暴露于合成抑制剂 ICI 182,780（ERβ 测定）或氟他胺（AR 测定）的情况下进行了共暴露。结果表明，雄激素作用是受体介导的，而雌激素作用可能仅部分通过受体介导。本研究表明，油类含有具有潜在内分泌干扰作用的化合物，其中一些通过激素受体起作用。
