Projects
08: Biological activity of complex mixtures of endocrine disruptors.
Biological activity of complex mixtures of endocrine disruptors.
The appearance of endocrine disruptors in our environment has been linked to an increased risk of cancer, reproductive disorders in humans and a loss of biodiversity in wildlife. Here, the biological effects and mechanism of action of endocrine disruptors will be determined by monitoring genome-wide changes of expression profiles in human cells.
Naegeli Hanspeter, Universität Zürich
e-mail: naegelih@pharm.unizh.ch
Background
Endocrine disruptors are defined as chemicals that disturb endogenous hormonal circuits and, hence, have deleterious effects in animals and humans. An unequivocal assessment of the hazards and magnitude of risk has not yet been possible due to insufficient knowledge of the extent of exposure to endocrine disruptors and their potential for adverse effects at low dose levels.
Aim
This project intends to determine the genomic effects of endocrine disruptors that have been shown to operate through the estrogen receptor system. Human cell lines expressing estrogen receptors will be exposed to xenobiotics with potential endocrine-disrupting activity which have been shown to occur in food, breast milk or other relevant sources. For this purpose, the transcriptional changes induced by endocrine disruptors or mixtures of these chemicals will be determined using high-density oligonucleotide DNA microarrays that cover the coding sequences of the entire human genome.
Significance
This project will contribute to the mechanistic knowledge of how endocrine disruptors reprogramme the genome of human target tissues. This knowledge will significantly help in elaborating regulatory measures that have to be taken in order to protect biodiversity and human health from the negative effects of endocrine disruptors. Furthermore, the results of this project are expected to initiate new strategies for screening chemicals. The use of appropriate experimental models with rapid testing procedures is likely to be of value to industry, since these methods allow the testing of chemicals during early screens. This information will be important in deciding which chemicals should be developed and evaluated further.