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ESTROGENIC ACTIVITY OF DICOFOL WITH THE HUMAN ESTROGEN RECEPTOR: ISOMER- AND ENANTIOMER-SPECIFIC IMPLICATIONS
Citation:
HOEKSTRA, P. F., B. K. BURNISON, A. W. GARRISON, T. NEHELI, AND D. C. MUIR. ESTROGENIC ACTIVITY OF DICOFOL WITH THE HUMAN ESTROGEN RECEPTOR: ISOMER- AND ENANTIOMER-SPECIFIC IMPLICATIONS. CHEMOSPHERE. Elsevier Science Ltd, New York, NY, 64(1):174-177, (2006).
Impact/Purpose:
To determine the environmental occurrences, fate, and effects of the enantiomers of selected chiral pesticides and other chiral pollutants.
Description:
Dicofol is a non-systemic acaricide/miticide currently registered in the U.S. 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 percent and 20 percent 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 (plus)-17-beta estradiol (positive control), p,p´-dicofol, racemic o,p´-dicofol [(plus minus)-o,p´-dicofol] and the individual o,p´-dicofol enantiomers was measured via quantification of beta-galactosidase. The (plus minus)-o,p´- and p,p´-dicofol were weak estrogen mimics (EC50: 4.2 × 10(-6) M and 1.6 × 10(-6) M, respectively) relative to estradiol (3.7 × 10(-10) M). For o,p´-dicofol, the beta-galactosidase induction by (-)-o,p´-dicofol (EC50: 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.