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[C]-苯并[a]芘在人体中的药代动力学:食用熏制三文鱼和限制苯并[a]芘饮食对其的影响。

Pharmacokinetics of [C]-Benzo[a]pyrene (BaP) in humans: Impact of Co-Administration of smoked salmon and BaP dietary restriction.

机构信息

Department of Nutrition and Dietetics, Oregon State University, Corvallis, OR, USA; Superfund Research Program, Oregon State University, Corvallis, OR, USA.

Superfund Research Program, Oregon State University, Corvallis, OR, USA; Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR, USA.

出版信息

Food Chem Toxicol. 2018 May;115:136-147. doi: 10.1016/j.fct.2018.03.003. Epub 2018 Mar 5.

Abstract

Benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), is a known human carcinogen. In non-smoking adults greater than 95% of BaP exposure is through diet. The carcinogenicity of BaP is utilized by the U.S. EPA to assess relative potency of complex PAH mixtures. PAH relative potency factors (RPFs, BaP = 1) are determined from high dose animal data. We employed accelerator mass spectrometry (AMS) to determine pharmacokinetics of [C]-BaP in humans following dosing with 46 ng (an order of magnitude lower than human dietary daily exposure and million-fold lower than animal cancer models). To assess the impact of co-administration of food with a complex PAH mixture, humans were dosed with 46 ng of [C]-BaP with or without smoked salmon. Subjects were asked to avoid high BaP-containing diets and a 3-day dietary questionnaire given to assess dietary exposure prior to dosing and three days post-dosing with [C]-BaP. Co-administration of smoked salmon, containing a complex mixture of PAHs with an RPF of 460 ng BaP, reduced and delayed absorption. Administration of canned commercial salmon, containing very low amounts of PAHs, showed the impacts on pharmacokinetics were not due to high amounts of PAHs but rather a food matrix effect.

摘要

苯并[a]芘(BaP)是一种多环芳烃(PAH),已知对人体有致癌性。在不吸烟的成年人中,超过 95%的 BaP 暴露是通过饮食。美国环保署利用 BaP 的致癌性来评估复杂 PAH 混合物的相对效力。PAH 相对效力因子(RPF,BaP=1)是根据高剂量动物数据确定的。我们采用加速质谱(AMS)技术,在人类摄入 46ng [C]-BaP 后,测定其体内的药代动力学,这一剂量比人类日常饮食中的 BaP 暴露量低一个数量级,比动物癌症模型中的 BaP 暴露量低百万倍。为了评估与复杂 PAH 混合物同时摄入食物对 BaP 吸收的影响,我们给人类摄入 46ng [C]-BaP,同时或不摄入熏三文鱼。要求研究对象避免高 BaP 含量的饮食,并在摄入 [C]-BaP 前和 3 天后进行 3 天的饮食问卷调查,以评估饮食暴露情况。同时摄入熏三文鱼,其中含有 RPF 为 460ng BaP 的复杂 PAH 混合物,会减少和延迟吸收。摄入罐装商业三文鱼,其中含有非常低水平的 PAH,表明这些对药代动力学的影响不是由于高含量的 PAH,而是由于食物基质的影响。

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