Toxification of polycyclic aromatic hydrocarbons by commensal bacteria from human skin

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-017-1964-3) contains supplementary material, which is available to authorised users.

Microbially competent 3D skin: a test system that reveals insight into host–microbe interactions and their potential toxicological impact

“…However, these models have not been pre-validated for toxicity studies. Also, the colonisation in these studies has been limited to 48-120 h. Yet, the studies of Sowada et al (2017) show that at least for PAHs microbe-mediated toxicity occurs predominantly at time-points later than 5 days. Moreover, the aforementioned models often lack a detailed biochemical characterisation (Bojar 2015;Cadau et al 2017;Holland et al 2008;Maboni et al 2017;Popov et al 2014).…”

Constraints and Priorities for Conducting Experimental Exposures of Marine Organisms to Microplastics

“…Conversely, large heteroaggregates may not be efficiently ingested, possibly explaining the accumulation of MP on the deep-sea floor in the absence of major grazing processes (Van Cauwenberghe et al, 2013). In addition, biofilm formation can (i) alter the diffusion of HOC from or into the particles as previously shown for passive samplers, usually made of PE, and glass beads (Wicke et al, 2008;Harman et al, 2009), and (ii) facilitate the metabolism of HOC leading to the degradation of bio-degradable contaminants including PAH, heavy metals, and pharmaceutical compounds and/or the production of metabolites of greater toxicity (Sowada et al, 2017;Tiwari et al, 2017). Therefore, this aspect should be taken into account in laboratory studies focusing on the role of MP in the transfer of contaminants into marine organisms/ecosystems.…”

Skin toxicology and 3Rs—Current challenges for public health protection

“…[103][104][105][106][107] The general metabolic competence of FT-models has previously been demonstrated with benzo[a]pyrene as the archetypic phase I-dependent procarcinogen. [108] Moreover, such models will also allow emulating the influence of the microbiome and its metabolism on skin toxicity, [24,[109][110][111] Having said that, it has to be noted that more complex does not necessarily mean better. Simple assays such as the NRU phototoxicity test do have their charm.…”