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Imprint
Dynamics and reaction of the microbial skin flora after exposure to different carbon sources on artificial skin models
Project
Project code: BfR-CPS-08-1322-656
Contract period: 01.01.2016
- 01.12.2017
Purpose of research: Basic research
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously occurring pollutants and contaminants, leading to frequent human exposure. Worryingly, especially high molecular weight PAHs possess an established potential as carcinogens or procarcinogens, respectively. In eukaryotes the underlying mechanisms are well-studied as is metabolic activation of model substances such as benzo[a]pyrene (B[a]P) by cytochrome P450-dependent oxygenases (CYPs). Recent studies now showed the human skin microbiome to also harbour potential for metabolic B[a]P-activation. However, unlike in eukaryotes activation is not the result of phase I detoxification gone wrong but occurs due to the excretion of genotoxic and cytotoxic metabolites in the course of bacterial B[a]P-degradation (Sowada et al. 2014; Sowada et al. unpublished). With up to 107 cfu/cm2 and more than 1000 microbial species the human skin is the second most densely populated human organ after the gut. At the same time it is also highly exposed to PAHs from air, commodities with skin contact or cosmetics, making the potential toxification of B[a]P by skin commensals relevant for human health (Sowada et al. 2014). Besides many substances already known from eukaryotes preliminary experiments confirmed the formation of several hitherto unkown B[a]P-metabolites. These included several B[a]P-diols, (hydroxylated) benzo[a]anthracene and phenanthrenecarboxylic acid. Synergistically these substances account for most of the cyto- and genotoxic effects observed in vitro. Given the potentially high toxicological relevance and our lack of knowledge regarding commensalic PAH-toxification this project hence aims to establish a co-culture system of bacterially competent 3D-skin models. This will not only allow for the first time to study PAH-metabolism and its potential effects in situ but will also be the basis for addressing questions of population dynamics or extended commensalic xenobiotic metabolism in general.
Section overview
Subjects
- Toxicology
