RELATIVE BINDING-AFFINITY SERUM MODIFIED ACCESS (RBA-SMA) ASSAY PREDICTS THE RELATIVE IN-VIVO BIOACTIVITY OF THE XENOESTROGENS BISPHENOL-A AND OCTYLPHENOL
Sc. Nagel et al., RELATIVE BINDING-AFFINITY SERUM MODIFIED ACCESS (RBA-SMA) ASSAY PREDICTS THE RELATIVE IN-VIVO BIOACTIVITY OF THE XENOESTROGENS BISPHENOL-A AND OCTYLPHENOL, Environmental health perspectives, 105(1), 1997, pp. 70-76
We have developed a relative binding affinity-serum modified access (R
BA-SIMA) assay to determine estrogen receptors within intact cultured
MCF-7 human breast cancer cells. We used this assay to predict low dos
e activity of two xenoestrogens in mice. In serum-free medium, bisphen
ol A, a component of polycarbonates and of resins used to line metal f
ood cans, showed a lower relative binding affinity (RBA; 0.006%) than
octylphenol (0.072%) and nonylphenol (0.026%), which are used as surfa
ctants in many commercial products (all RBAs are relative to estradiol
, which is equal to 100%). In 100% serum from adult men, bisphenol A s
howed a higher RBA (0.01%) than in serum-flee medium and thus enhanced
access to estrogen receptors relative to estradiol. In contrast, octy
lphenol showed a 22-fold decrease in RBA (0.0029%) and nonylphenol sho
wed a 5-fold decrease in RBA (0.0039%) when measured in adult serum. T
his indicates that, relative to estradiol, serum had less of an inhibi
tory effect on the cell uptake and binding in MCF-7 cells of bisphenol
A, while serum had 2 greater inhibitory effect on octylphenol and non
ylphenol relative to estradiol. Extrapolation of these relative activi
ties in adult serum predicted that the estrogenic bioactivity of bisph
enol A would be over 500-fold greater than that of octylphenol in feta
l mouse serum. Bisphenol A and octylphenol were fed to pregnant mice a
t 2 and 20 mu g/kg/day. Exposure of male mouse fetuses to either dose
of bisphenol A, but to neither dose of octylphenol, significantly incr
eased their adult prostate weight relative to control males, which is
consistent with the higher predicted bioactivity of bisphenol A than o
ctylphenol in the RBA-SMA assay. In addition, our findings show for th
e first time that fetal exposure to environmentally relevant parts-per
-billion (ppb) doses of bisphenol A, in the range currently being cons
umed by people, can alter the adult reproductive system in mice.