RELATIVE BINDING-AFFINITY SERUM MODIFIED ACCESS (RBA-SMA) ASSAY PREDICTS THE RELATIVE IN-VIVO BIOACTIVITY OF THE XENOESTROGENS BISPHENOL-A AND OCTYLPHENOL

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.