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Oral exposure to PAH: bioactivation processes in the human gut

机译:口服PAH:人体肠道的生物激活过程

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摘要

We used the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) to perform in vitro stomach, small intestine and colon digestion experiments on polycyclic aromatic hydrocarbons (PAH) as pure compounds or from contaminated environmental samples entering the gastrointestinal tract. To screen for possible toxicological aspects, two yeast bioassays were used on the digests. Binding of PAHs to the human aryl hydrocarbon receptor (hAR) and binding of probable PAH biotransformation products to the human estrogen receptor (hER) was evaluated in the aryl yeast and estrogen yeast assay, respectively. Upon incubation with colon microbiota, positive signals in the estrogen receptor test were observed. PAHs as such are not estrogenic, leading to our hypothesis that biotransformation reactions had occurred during incubation with colon micro-biota in the SHIME reactor. The production of intermediates that have already been described to have estrogenic or genotoxic properties, was confirmed by the detection of 1-hydroxypyrene and 7-hydroxybenzo(a)pyrene using LC-ESI-MS.
机译:我们使用人类肠道微生物生态系统(SHIME)模拟器对多环芳烃(PAH)的纯净化合物或受污染的进入胃肠道的环境样品进行了体外胃,小肠和结肠消化实验。为了筛选可能的毒理学方面,在消化物中使用了两种酵母生物测定法。分别在芳基酵母和雌激素酵母试验中评估了PAHs与人芳烃受体(hAR)的结合以及PAH生物转化产物可能与人雌激素受体(hER)的结合。与结肠菌群温育后,在雌激素受体测试中观察到阳性信号。这样的PAH并不是雌激素,导致我们的假设是在SHIME反应器中与结肠微生物群落孵育期间发生了生物转化反应。通过使用LC-ESI-MS检测1-羟基py和7-羟基苯并(a)re,证实了已描述具有雌激素或遗传毒性性质的中间体的生产。

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