The effects of PAHs and N-PAHs on retinoid signaling and Oct-4 expression in vitro
| Autor: | Martin Beníšek, Luděk Bláha, Klára Hilscherová, Petra Kubincová |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
medicine.drug_class
Cell Survival Cellular differentiation Blotting Western Retinoic acid Down-Regulation Gene Expression Tretinoin 010501 environmental sciences Biology Retinoid X receptor Toxicology 01 natural sciences Xenobiotics 03 medical and health sciences chemistry.chemical_compound Mice Retinoids Downregulation and upregulation Genes Reporter Heterocyclic Compounds Cell Line Tumor medicine Animals Retinoid Polycyclic Aromatic Hydrocarbons Luciferases 030304 developmental biology 0105 earth and related environmental sciences 0303 health sciences Reporter gene organic chemicals General Medicine Aryl hydrocarbon receptor Cell biology Up-Regulation Biochemistry chemistry biology.protein Environmental Pollutants Signal transduction Octamer Transcription Factor-3 |
| Zdroj: | Toxicology letters. 200(3) |
| ISSN: | 1879-3169 |
| Popis: | Polycyclic aromatic hydrocarbons (PAHs) and their N-heterocyclic analogs (N-PAHs) are important environmental contaminants with negative effects in living organisms, including teratogenicity and embryotoxicity. Though most studies linked their embryotoxicity with aryl hydrocarbon receptor (AhR) and cytochrome P450 activation, the exact mechanism is not known. Other mechanisms such as disruption of retinoid signaling were recently suggested to be of importance. This study investigated PAHs and N-PAHs interference with retinoid signaling in vitro by modulating all-trans retinoic acid (ATRA) mediated response in a reporter gene assay using P19/A15 cell line. Further, effects on pluripotency and differentiation processes were evaluated by measuring octamer-4 (Oct-4), an important pluripotency marker and master differentiation factor. Two of the studied compounds, benz[a]anthracene and benz[c]acridine significantly up-regulated ATRA-mediated response in the co-exposure with a range of ATRA concentrations. Another structural N-PAH variant, 1,7-phenanthroline, downregulated ATRA-mediated response at most of tested ATRA concentrations and exposure times. Interesting concentration-dependent biphasic effects (i.e. downregulation with subsequent up-regulation to control levels) were observed at co-exposures of ATRA and parent PAH phenanthrene. Non significant Oct-4 modulation in co-exposure with ATRA was observed at compounds, which potentiated ATRA-mediated effects in the reporter gene assay. On the other hand, 1,7-phenanthroline and phenanthrene significantly suppressed Oct-4 levels in higher tested concentrations. Our results further extend the knowledge of PAH and N-PAH in vitro effects and indicate that these environmental toxicants may have influence on differentiation process and embryonic development by interfering with ATRA signaling and by modulating levels of Oct-4. |
| Databáze: | OpenAIRE |
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