Mittwoch, 29. November 2017, 17:00 - 18:30 iCal

Prof. Jan Vondracek

Department of Cytokinetics at the Institute of Biophysics, Czech Academy of Sciences, Brno, Czech Republic


"Cellular microenvironment and its role in epigenetic regulation of CYP1 enzymes expression and activity"

Joseph Loschmidt Hörsaal der Fakultät für Chemie
Währinger Straße 42, 1090 Wien


Cellular microenvironment and its role in epigenetic regulation of CYP1 enzymes expression and activity


Polycyclic aromatic hydrocarbons (PAHs) represent a highly diverse group of environmental pollutants that includes both low-molecular-weight compounds with limited genotoxicity and the higher-molecular-weight contaminants, which interact with multiple intracellular receptors and may form genotoxic metabolites inducing DNA damage and activating DNA damage response in target cells. The presentation is intended to provide an overview of some our recent experi-mental studies evaluating the interactions of PAHs with intracellular signaling modules in epithelial cells, as well as to comment on the consequences of these interactions for the molecular mechanisms relevant for the toxicity of PAHs. Using benzo[a]pyrene (BaP), a prominent carcinogenic PAH as a model compound, we examined how the inflammatory signaling, disruption of key pathways involved in oncogenic signaling, or microbiome-derived dietary factors (such as short-chain fatty acids that are produced by anaerobic bacterial fermentation of dietary fiber) can modulate metabolic activation of BaP via deregulation of expression and activity of various cytochrome P450 family 1 (CYP1) enzymes. We show that, despite acting via different mechanisms, all of these factors may significantly modulate toxicity of BaP and/or related pollutants in target cells in vitro. Interestingly, we found that various mechanisms linked with regulation of his-tone post-translational modifications (including e.g. p38 MAP kinase signaling or deregulation of histone acetylation) may have profound effects on toxicity of PAHs or related environmental/dietary contaminants.


Fakultät für Chemie, Institut für Lebensmittelchemie und Toxikologie


Brigitte Schwarz
Fakultät für Chemie der Universität Wien