title: Biomarkers of endocrine disruption: cluster analysis of effects of plasticisers on Phase 1 and Phase 2 metabolism of steroids.
abstract: Although some endocrine disruptors (EDs) act at steroid receptors, it is now apparent that compounds may have ED potential if they alter steroid synthesis or metabolism, particularly if they affect Phase 1 or Phase 2 pathways. In the ENDOMET project (EU-funded 5th Framework programme), 23 different assays were used on a wide range of EDs. Cluster analysis of the matrix results enabled identification of four integrated test systems that can be used to pinpoint compounds that are able to alter steroid metabolism or function. Critical pathways were shown to include oestrogen synthesis and sulphonation, synthesis of sulphate/PAPS and thyroid hormone regulation so that the activity profiles of some Phase 1 and Phase 2 reactions can be used as biomarkers for detection of compounds with ED potential.
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham, UK. r.h.waring@bham.ac.uk
authors.forename: R H
authors.initials: RH
authors.lastname: Waring
authors.forename: D B
authors.initials: DB
authors.lastname: Ramsden
authors.forename: P D B
authors.initials: PD
authors.lastname: Jarratt
authors.forename: R M
authors.initials: RM
authors.lastname: Harris
mesh_terms: D000465:Algorithms; D015415:Biomarkers / Q000378:metabolism*; D016000:Cluster Analysis; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004785:Environmental Pollutants / Q000032:analysis / Q000494:pharmacology; D005062:European Union; D015894:Genome, Human / Q000187:drug effects; D020723:Glucuronic Acid / Q000378:metabolism; D006801:Humans; D007391:International Cooperation; D010724:Phosphoadenosine Phosphosulfate / Q000378:metabolism; D010968:Plasticizers / Q000494:pharmacology*; D011987:Receptors, Steroid / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: D015415:Biomarkers; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D010968:Plasticizers; D011987:Receptors, Steroid; D013256:Steroids; D013963:Thyroid Hormones; D010724:Phosphoadenosine Phosphosulfate; D020723:Glucuronic Acid; D003577:Cytochrome P-450 Enzyme System; D015238:Sulfotransferases