Estrogenic activity of dicofol with the human estrogen receptor: Isomer- and enantiomer-specific implications
| Autor: | A. Wayne Garrison, Tannis Neheli, Paul F. Hoekstra, B. Kent Burnison, Derek C. G. Muir |
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| Rok vydání: | 2006 |
| Předmět: |
Transcriptional Activation
Agonist Insecticides Environmental Engineering medicine.drug_class Stereochemistry Health Toxicology and Mutagenesis Estrogen receptor Saccharomyces cerevisiae chemistry.chemical_compound Stereospecificity Isomerism Endocrine disrupting compound medicine Humans Environmental Chemistry Dicofol Estrogens Non-Steroidal Chemistry Public Health Environmental and Occupational Health General Medicine General Chemistry beta-Galactosidase Pollution Receptors Estrogen Estrogen Racemic mixture Enantiomer |
| Zdroj: | Chemosphere. 64:174-177 |
| ISSN: | 0045-6535 |
| Popis: | Dicofol is a non-systemic acaricide/miticide currently registered in the US and Canada for use on a wide variety of crops. This agrochemical has been identified as a potential candidate substance for the United Nations Economic Commission for Europe (UN-ECE) Persistent Organic Pollutant (POP) Protocol and implicated as a potential “endocrine disrupting compound”. The technical product is usually synthesized from technical DDT and consists of approximately 80% and 20% of p , p ′- and o , p ′-dicofol isomers. The o , p ′-substituted isomer of dicofol is chiral and may have enantiomer-specific activity; however, the stereospecific activity of o , p ′-dicofol has not been reported. In this study, we examined the isomer- and enantiomer-specific endocrine disruption potential of dicofol using yeast-based steroid hormone receptor gene transcription assay designed with the human estrogen receptor (hER). Estrogenic activity of (+)-17-β estradiol (positive control), p , p ′-dicofol, racemic o , p ′-dicofol [(±)- o , p ′-dicofol] and the individual o , p ′-dicofol enantiomers was measured via quantification of β-galactosidase. The (±)- o , p ′- and p , p ′-dicofol were weak estrogen mimics (EC 50 : 4.2 × 10 −6 and 1.6 × 10 −6 M, respectively) relative to estradiol (3.7 × 10 −10 M). For o , p ′-dicofol, the β-galactosidase induction by (−)- o , p ′-dicofol (EC 50 : 5.1 × 10 −7 M) was greater than the racemic mixture. However, the (+)- o , p ′-dicofol enantiomer was found to have negligible estrogenic activity. These data indicate that dicofol is a weak hER agonist due to activity of the achiral p , p ′-isomer and (−)- o , p ′-substituted enantiomer and emphasizes the influence of chemical structure and configuration on biological responses to exposure from chiral compounds. |
| Databáze: | OpenAIRE |
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