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Imprint
Biomarkers for the human internal exposure to pyrrolizidine alkaloids
Project
Project code: BfR-LMS-08-1322-641
Contract period: 01.03.2016
- 31.12.2016
Purpose of research: Applied research
Pyrrolizidine alkaloids (PAs) are a class of diverse secondary plant metabolites, among them many carcinogenic agents. They are metabolically activated by cytochrome P450 (CYP)-catalyzed oxidation to reactive esters of (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP, or dehydroretronecine/dehydroheliotridine), which may modify DNA and proteins by formation of covalent bonds. Also DHP itself or its glutathione conjugates are DNA-reactive and form adducts that structurally match those of the related reactive DHP esters. The aim of this project is to develop analytical methods for the determination of protein adducts and of urinary excretion products of DHP. The amounts of DHP-adducts in blood proteins reflect the internal exposure to reactive PAs over several weeks, while urinary analytes, e.g. putative mercapturic acids of DHP are potential descriptors for the short-term PA uptake. These biomarkers may be used to investigate possible correlations between the internal PA exposure and disease in future molecular epidemiological studies.
Section overview
Subjects
- Food Chemistry
- Toxicology
