Interaction between metabolism and transport of toxicological relevant compounds in the gastrointestinal barrier

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-08-1350-003
Contract period: 01.12.2005 - 31.03.2009
Purpose of research: Applied research

The interaction between the cytochrome P450-system, phase II xenobiotic-metabolizing enzymes (XMEs) such as glutathione-S-transferases, UDP-glucuronosyl transferases and sulfotransferases, and ABC-transport proteins is an important part of the mucosa of the small intestine acting as a potential biochemical barrier for nutritional- and eco-toxicological relevant compounds. Intestinal resorption of cancerogenic contaminants of food such as the polycyclic aromatic hydrocarbon (PAHs) benzo[a]pyrene (B[a]P) is affected by the interaction of CYP1A1/CYP1B1, phase II XMEs and ABC-transport proteins. It was shown that excretion of the B[a]P phase II metabolites including B[a]P-glucuronides and B[a]P-sulfates is mediated by breast cancer resistance protein (BCRP) (Ebert et al., 2005). In the project we here apply for the mechanism of detoxification of the ultimate carcinogenic phase I B[a]P metabolite anti-B[a]P-7,8-diol-9,10-epoxide (BPDE) will be studied. Formation of glutathione conjugates mediated by glutathione-S-transferases (GSTs) as well as the excretion of these conjugates will be analysed. Our studies will focus on the identification of transport proteins that are involved in GSH conjugate excretion.

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