• P. Chr. de Jong, M.D., Ph.D., Antonius Hospital Nieuwegein, University Medical Center Utrecht, Nieuwegein, The Netherlands.
• P.H.M. Peeters, Ph.D., Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht.
• Prof. M.S. Denison, Ph.D., Departement of Environmental Toxicology, University of California, Davis, USA.
• Chulabhorn Royal Research Institute, Bangkok, Thailand.

This research focuses on the development of bioassays to study (natural or synthetic) xenobiotic-induced endocrine toxicology. These models are used to study mechanisms of action of (natural or synthetic) compounds and their potential effect on hormone-dependent tumors.

Cell culture with cell lines and primary (human) tissues, various molecular biological techniques such as enzyme activity assays, DNA/RNA isolation, RT-PCT, gel electrophoresis, Western blotting. Receptor-binding assays using recombinant bioassays. Measurement of cell viability, cell cycle status and apoptosis.

During the past years, a shift in cancer research interest is seen from the treatment of cancer toward the prevention of cancer. For chemoprevention, intervention of biological processes involved in carcinogenesis requires modulation of molecular targets. Some classess of phytochemicals (chemicals derived from plants) appear to be suitable for this purpose, since they are biologically active compounds that occur in our daily diet. The suggested chemopreventive actions of phytochemicals are often attributed to their ability to bind to the estrogen receptor. However, phytochemicals can possibly influence the intiation, promotion or proliferation of hormone-dependent tumors, such as breast cancer, at multiple levels. Our research focuses on the mechanism of action of a wide variety of phytochemicals and their potential role in chemoprevention of hormone-dependent cancer.

It must be recognized that in vitro endocrine toxicology studies are complex and that extrapolation of data can only be as good as the experimental model. One of the difficulties of studying hormonal responsiveness, for example in breast tissue, is the lack of tissue microenvironment and the lack of all the complex physiological regulatory mechanisms that exist in vivo. However, using human cells and primary tissues in more complex systems (such as co-culture of multiple cell types), allows a better interpretation and extrapolation of the in vitro findings to the in vivo, human situation.