Project of Suzanne Jeurissen and Frank Claassen
Project title: Dietary risks and ingredient interactions between (anti)carcinogens from herbs

Safrole, methyleugenol and estragole are alkenylbenzenes that are important constituents of herbs like basil, nutmeg and anise. Methyleugenol and estragole are also used as flavouring agent in a variety of dietary products. Recently the EU Scientific Committee on Food (EU-SCF) has launched scientific evaluations on these compounds and concluded that the compounds mentioned are genotoxic and carcinogenic. Therefore, restrictions in use were indicated by the EU-SCF. Safrole has already been banned as a food additive by the Council of the European Communities and by the US Food and Drug Administration. Since carcinogenicity of these compounds was demonstrated in animal experiments using relatively high doses of single compounds, the assessment of human health hazard posed by consuming these compounds in a matrix of herbal food ingredients is complex and merits further attention.

The first goal of this PhD-project is to identify the cytochrome P450 enzymes that catalyse the bioactivation of these compounds to their proximate carcinogenic 1'-hydroxymetabolites. For safrole, these enzymes are identified (Jeurissen et al. Chem. Res. Toxicol. 2004, 17, 1245-1250) and for the other compounds the studies are underway.

Insight in the P450 enzymes responsible for the bioactivation of these compounds will be used to identify the inhibitors of these P450 enzymes in extracts from the herbs. The second goal of this PhD-project is to set-up an HPLC on-line detection system. In this system HPLC separation of herbal extracts will be coupled to an on-line inhibition assay for P450  activity.
 

Scheme of on-line detection set-up for potentially anticarcinogenic compounds

Results from these experiments will ultimately be used to gain insight in the composition of the carcinogenic and (anti)carcinogenic compounds in different herbs. This knowledge is essential for a balanced risk-benefit evaluation of these herbs.

This Ph.D. project is carried out in close cooperation with the Laboratory of Toxicology of Wageningen University (Prof. Ivonne Rietjens).