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人皮肤共生细菌对多环芳烃的毒化作用。

Toxification of polycyclic aromatic hydrocarbons by commensal bacteria from human skin.

作者信息

Sowada Juliane, Lemoine Lisa, Schön Karsten, Hutzler Christoph, Luch Andreas, Tralau Tewes

机构信息

Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany.

出版信息

Arch Toxicol. 2017 Jun;91(6):2331-2341. doi: 10.1007/s00204-017-1964-3. Epub 2017 Apr 4.

Abstract

The ubiquitous occurrence of polycyclic aromatic hydrocarbons (PAHs) leads to constant human exposure at low levels. Toxicologically relevant are especially the high-molecular weight substances due to their (pro-)carcinogenic potential. Following ingestion or uptake, the eukaryotic phase I metabolism often activates these substances to become potent DNA binders, and unsurprisingly metabolism and DNA-adduct formation of model substances such as benzo[a]pyrene (B[a]P) are well studied. However, apart from being subjected to eukaryotic transformations PAHs are also carbon and energy sources for the myriads of commensal microbes inhabiting man's every surface. Yet, we know little about the microbiome's PAH-metabolism capacity and its potentially adverse impact on the human host. This study now shows that readily isolable skin commensals transform B[a]P into a range of highly cyto- and genotoxic metabolites that are excreted in toxicologically relevant concentrations during growth. The respective bacterial supernatants contain a mixture of established eukaryotic as well as hitherto unknown prokaryotic metabolites, the combination of which leads to an increased toxicity. Altogether we show that PAH metabolism of the microbiome has to be considered a potential hazard.

摘要

多环芳烃(PAHs)的广泛存在导致人类持续低水平接触。从毒理学角度来看,尤其高分子量物质因其(潜在的)致癌潜力而备受关注。摄入或吸收后,真核生物的I相代谢通常会将这些物质激活为强效的DNA结合剂,毫不奇怪,诸如苯并[a]芘(B[a]P)等模型物质的代谢及DNA加合物形成已得到充分研究。然而,除了经历真核生物转化外,PAHs还是栖息在人体各个表面的大量共生微生物的碳源和能源。然而,我们对微生物群落的PAH代谢能力及其对人类宿主潜在的不利影响知之甚少。这项研究表明,易于分离的皮肤共生菌将B[a]P转化为一系列具有高度细胞毒性和遗传毒性的代谢产物,这些代谢产物在生长过程中以毒理学相关浓度排出。相应的细菌上清液含有已确定的真核生物代谢产物以及迄今未知的原核生物代谢产物的混合物,它们的组合导致毒性增加。总之,我们表明微生物群落的PAH代谢必须被视为一种潜在危害。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22bc/5429354/0bdeb57cc40a/204_2017_1964_Fig1_HTML.jpg

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