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Effects of natural occuring fatty acids on the bioavailability and the metabolism of polycyclic aromatic hydrocarbons by taking the example of benzo[a]pyrene

Project

Food and consumer protection

This project contributes to the research aim 'Food and consumer protection'. Which funding institutions are active for this aim? What are the sub-aims? Take a look:
Food and consumer protection


Project code: BfR-LMS-08-1322-544
Contract period: 01.03.2013 - 31.12.2016
Purpose of research: Applied research

The polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P) is an ubiquitous occurring environmental contaminant primary ingested with food. B[a]P is generated during broiling meat or curing. The resorption of B[a]P is depending on the dose and the matrix ingested with. The bioavailability is increased by a simultaneous ingest of fat and decreased by dietary fibers. It was recently published that the fatty acid oleic acid decreases the gene expression of the ABC-transporter ABCG2 resulting in an decreased efflux of the ABCG2 substrate mitoxantrone (Aspenstroem-Fagerlund et al., 2011). ABCG2 also transports phase II conjugates of B[a]P resulting in a reduction of the oral bioavailability of this carcinogenic environmental contaminant. The aim of this study is to elucidate the molecular mechanisms of a simultaneous uptake of the main nutritional fatty acids (myrisitic, palmitic, stearic, oleic, linoleic, linolenic acid) and the efflux of B[a]P and its metabolites in a model system of the human intestinal barrier (Caco-2 cell model). This includes the effect of the fatty acids on the cell viability of differentiated Caco-2 cells as well as on the gene expression profile of important intestinal efflux carrier involved in the reduction of the oral bioavailability of xenobiotics. This project shall clarify mechanisms of a co-uptake and additionally, enhance the understanding of the interaction of natural nutritive components and food contaminants. The polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BP) is a ubiquitously occurring environmental contaminant primary ingested with food. BP is generated during broiling meat or curing. During broiling, complex mixtures of PAH are generated with fluoranthene (297 µg/kg), pyrene (354 µg/kg) and BP (157 µg/kg) representing the three most frequent PAH. Effects of this mixture on the molecular mode of action and the metabolism of the pro-carcinogenic BP are not well investigated yet. Therefore, this study should contribute to a better understanding of the induction of cytotoxicity, induction of gene expression of BP-relevant enzymes and the induction of nuclear receptors if BP occurs in mixture. Our experiments revealed weak effects on cell viability in HepG2, HEK293, or Caco-2 cells independent of cell exposure. In Caco-2 cells, an inhibitory effect on mRNA expression was detected after the exposure to BP in mixture compared to the BP mono-exposure. However, analysis of the activation of the AhR did not show an inhibition of activation after treatment with BP in mixture. Strong effects were observed for the transactivation of CAR: the non-carcinogenic PYR and FLU strongly activated CAR, but in co-exposure the effect seem to be decreased. The results of the effects on the metabolism if BP occurs in mixture are still pending. In summary the results of this study show that the uptake of the food carcinogen BP in mixture caused effects at the molecular level. We observed an inhibition of molecular effects like the induction of CYP1A1. However, for more comprehensive further endpoints should be investigated.

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Framework programme

BMEL Frameworkprogramme 2008

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