There is a growing concern that environmental xenobiotics may be affecting
human and wildlife health by disrupting normal endocrine function via inter
action with steroid hormone receptors. Several of these persistent contamin
ants are chiral and may have enantiomer-specific biological properties. Pre
vious experiments have demonstrated that (-)-o,p'-DDT enantiomer is a more
active estrogen-mimic than the (+)-enantiomer in rats. However, these resul
ts have not been extrapolated to other biological systems. This study used
a yeast-based assay to assess the enantiomer-specific transcriptional activ
ity of DDT with the human estrogen receptor (hER). (+)-17 beta -estradiol,
racemic DDT and individual DDT enantiomers were added to yeast cultures and
hER activity was measured by quantification of P-galactosidase. The relati
ve activity of o,p'-DDT was weak compared to estradiol. For o,p'-DDT, the (
-)-enantiomer was the active estrogen mimic whereas the hER activity of ()-o,p'-DDT was negligible. The presence of the ( +)-enantiomer at relativel
y greater concentration decreased the transcriptional activity of ( -)-o,p'
-DDT. This data demonstrates the need to consider stereochemistry of enviro
nmental contaminants and their potential influence on biological responses.
(C) 2001 Elsevier Science Ireland Ltd. All rights reserved.