| A binary screening assay for pro-oestrogens in food: metabolic activation using hepatic microsomes and detection with oestrogen sensitive recombinant yeast cells. | |
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MedLine Citation:
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PMID: 12623674 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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An assay, employing microsomes prepared from rat liver and a recombinant cell bioassay (RCBA) expressing the human oestrogen receptor (alpha) linked to a reporter gene, was evaluated for the detection of pro-oestrogens in food using methoxychlor and mestranol as model compounds. Bio-activation of the hop phytoestrogen isoxanthohumol to the potent oestrogen 8-prenylnaringenin was also investigated. The oestrogenic potency values for reference standards determined with the RCBA (17beta-oestradiol = 100%) were: methoxychlor 0.0025%, mestranol 1.3%, isoxanthohumol 0.001%, and for their potential respective metabolites were: bishydroxymethoxychlor 0.015%, 17alpha-ethynyl oestradiol 69% and 8-prenylnaringenin 0.4%. Incubation of methoxychlor and mestranol (10 microM) with microsomes prepared from the liver of rats treated with Aroclor 1254 significantly increased (p < 0.001) their oestrogenic potency from 0.0021 and 2.4% to 0.015 and 8.3%, respectively. In contrast, the potency of the hop phytoestrogen isoxanthohumol was unchanged. Metabolites were identified by UV-HPLC-MS/MS as monohydroxy methoxychlor and HPTE from methoxychlor, and the major metabolite of mestranol was 17alpha-ethynyl oestradiol. There was no evidence for the metabolism of isoxanthohumol. Mestranol was also activated by microsomes induced with saline (control), beta-napthoflavone, 3-methylcholantherene, isoniazid or pregnenolone-16alpha-carbonitrile, but not phenobarbitone. These studies demonstrate the principle for use of a binary assay system for the detection of pro-oestrogens and indicate the potential value for risk assessment of endocrine disrupting chemicals. |
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Authors:
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N G Coldham; R Horton; M F Byford; M J Sauer |
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Publication Detail:
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Type: Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Food additives and contaminants Volume: 19 ISSN: 0265-203X ISO Abbreviation: Food Addit Contam Publication Date: 2002 Dec |
Date Detail:
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Created Date: 2003-03-07 Completed Date: 2003-03-26 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8500474 Medline TA: Food Addit Contam Country: England |
Other Details:
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Languages: eng Pagination: 1138-47 Citation Subset: IM |
Affiliation:
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Department of Risk Research, Veterinary Laboratories Agency, Addlestone, Surrey KT15 3NB, UK. n.g.coldham@vla.defra.gsi.gov.uk |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biological Assay / methods Biotransformation Chromatography, High Pressure Liquid / methods Estradiol Congeners / analysis*, pharmacokinetics Estrogen Receptor alpha Food Analysis / methods* Food Contamination / analysis* Genes, Reporter Humans Insecticides / analysis Mestranol / analysis Methoxychlor / analysis Microsomes, Liver / metabolism Rats Receptors, Estrogen / genetics Yeasts / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Estradiol Congeners; 0/Estrogen Receptor alpha; 0/Insecticides; 0/Receptors, Estrogen; 72-33-3/Mestranol; 72-43-5/Methoxychlor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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