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Listen to this siteWednesday 14 July 2004
This research project aims to examine the mechanism of action of dietary phytoestrogens by looking at gene expression after exposure to these compounds.
Study Duration : April 2000 to July 2003
A detailed understanding of the effects of dietary phytoestrogens on gene expression is required to determine the possible health effects (both harmful and beneficial) of consuming these compounds. It is thought that phytoestrogens could affect the body by mimicking or blocking the action of the human hormone oestrogen, or via other mechanisms such as antioxidant activity. This project aims to determine what effects phytoestrogens have on gene expression in relation to those of oestrogen.
The effects of oestrogen and one phytoestrogen, genistein, on gene expression will be determined in an oestrogen responsive model system (the uterus) and in cultured human cells.
In the model system (the uterus), genistein was found to affect the expression of the same set of genes as oestrogen. This suggests that genistein may be able to mimic oestrogen within the body. However, the concentration of genistein used was over 600-fold greater than that of oestrogen (i.e. 250 mg/kg genistein compared to 400 µg/kg oestrogen). Furthermore, the amount of genistein administered was significantly higher than the level that would be attained within the human body from normal dietary intake. Genistein was not found to elicit biological effects through mechanisms unrelated to oestrogenic activity.
The results obtained using the model system of the uterus were confirmed using cultured human cells treated with 10 -5 M genistein and 10 -8 M oestrogen.
The results of this project were evaluated by the Committee on Toxicity as part of its review on phytoestrogens and health. .
The final report is available from the FSA Library and Information centre.
To obtain a copy, please contact the Enquiry Desk, Dr Elsie Widdowson Library and Information Services, Food Standards Agency ( tel: 020 7276 8181/8182 or email:
library&info@foodstandards.gsi.gov.uk
)
Publications:
Murphy, T.C. and Orphanides, G. (2002). Characterisation of the molecular responses to xenoestrogens using gene expression profiling. Phytochemistry Reviews 1, 199-208.
Presentations:
Use of gene expression profiling to understand the transciptional programme associated with estrogen-induced uterine growth: implications for the use of surrogate markers in toxicology. SCOP/IUPAC meeting, Yokohama 2002.
Use of gene expression profiling in mechanistic toxicology. Toxicogenomics Gordon Conference, Maine 2003 .
Use of gene expression profiling to understand the transcriptional programme associated with estrogen-induced uterine growth: implications for the use of surrogate molecular markers in toxicology. US Society of Toxicology Annual Meeting, Salt Lake City 2003 .
How do natural and synthetic estrogens induce cell proliferation and differentiation? A transcriptional view of the uterotrophic response. EuroTox Annual Meeting, Florence 2003.
Contact
:
Email
: science@foodstandards.gsi.gov.uk
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