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Identification of molecular markers of effect of toxicologically relevant compounds to support human biomonitoring

Project


Project code: BfR-LMS-08-1322-710
Contract period: 01.09.2018 - 31.12.2019
Purpose of research: Applied research

Human biomonitoring is a strategy to measure the real, internal exposure against environmental factors including nutrition. Goals are the detection of exposure, the analysis of effects on human health, as well as the discovery of pollutant-related diseases with the help of biomarkers. Humans are exposed to a variety of genotoxins via different paths of exposure, including food intake. Therefore the development of a universal screening method makes sense, which is suited to detect effects of all relevant factors as well as possible combination effects resulting from exposure to genotoxic mixtures. Gene expression analyses appear to be a promising novel tool for effect monitoring. In medicine, mRNA transcripts are already used as biomarkers for diagnosis and treatment of certain diseases, and toxicologists have shown the value of transcript patterns to stratify different classes of toxins. Various genotoxic carcinogens are found in foodstuff. These are frequently consumed together, e.g. with grilled meat. Genotoxic compounds of different classes are formed as process contaminants during food preparation, e.g. nitrosamines, heterocyclic aromatic amines, or polycyclic aromatic hydrocarbons. Numerous of these compounds are classified as (putative) human carcinogens. In addition, there are also plant-derived carcinogens: secondary platn metabolites that have shown tumor-inducing properties in animal studies are found in spices. Phenylpropanoids such as eugenol, methyleugenol, estragol or safrole, are constituents of ethereous oils, fennel, basil, or nutmeg. Pyrrolizidine alkaloids are also liver toxic. Aflatoxin B1 is a well-known liver tumor-inducing mycotoxin produced by Aspergillus flavus, a fungus preferentially found on nuts. Goal of the project is the development of RNA effect marker patterns in liver and blood cells to support human biomonitoring. These effect marker patterns will help to solve questions related to the correlation of effects in blood cells and target organ (liver), and will be tested for their suitability to the detection of genotoxic mixture effects in the target organ via the observed effects in blood cells. Representatives of the abovementioned food-relevant chemical classes will be used as test substances for the study.

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Framework programme

BMEL - research cluster

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