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Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol.
Open accessAbstract
We have developed a relative binding affinity-serum modified access (RBA-SMA) assay to determine the effect of serum on the access of xenoestrogens to estrogen receptors within intact cultured MCF-7 human breast cancer cells. We used this assay to predict low dose activity of two xenoestrogens in mice. In serum-free medium, bisphenol A, a component of polycarbonates and of resins used to line metal food cans, showed a lower relative binding affinity (RBA; 0.006%) than octylphenol (0.072%) and nonylphenol (0.026%), which are used as surfactants in many commercial products (all RBAs are relative to estradiol, which is equal to 100%). In 100% serum from adult men, bisphenol A showed a higher RBA (0.01%) than in serum-free medium and thus enhanced access to estrogen receptors relative to estradiol. In contrast, octylphenol showed a 22-fold decrease in RBA (0.0029%) and nonylphenol showed a 5-fold decrease in RBA (0.0039%) when measured in adult serum. This indicates that, relative to estradiol, serum had less of an inhibitory effect on the cell uptake and binding in MCF-7 cells of bisphenol A, while serum had a greater inhibitory effect on octylphenol and nonylphenol relative to estradiol. Extrapolation of these relative activities in adult serum predicted that the estrogenic bioactivity of bisphenol A would be over 500-fold greater than that of octylphenol in fetal mouse serum. Bisphenol A and octylphenol were fed to pregnant mice at 2 and 20 micrograms/kg/day. Exposure of male mouse fetuses to either dose of bisphenol A, but to neither dose of octylphenol, significantly increased their adult prostate weight relative to control males, which is consistent with the higher predicted bioactivity of bisphenol A than octylphenol in the RBA-SMA assay. In addition, our findings show for the first time that fetal exposure to environmentally relevant parts-per-billion (ppb) doses of bisphenol A, in the range currently being consumed by people, can alter the adult reproductive system in mice.
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Cited by
Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses
Vandenberg, L. N., Colborn, T., Hayes, T. B., Heindel, J. J., Jacobs, D. R., Lee, D.-H., Shioda, T., Soto, A. M., vom Saal, F. S., Welshons, W. V., et al. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1050 · Cited by 3,209
Self-citationIn vivo effects of bisphenol A in laboratory rodent studies
Richter, C. A., Birnbaum, L. S., Farabollini, F., Newbold, R. R., Rubin, B. S., Talsness, C. E., Vandenbergh, J. G., Walser-Kuntz, D. R., & vom Saal, F. S. (2007) · Reproductive Toxicology · doi:10.1016/j.reprotox.2007.06.004 · Cited by 1,147
Self-citationUrinary Concentrations of Bisphenol A and 4-Nonylphenol in a Human Reference Population
Calafat, A. M., Kuklenyik, Z., Reidy, J. A., Caudill, S. P., Ekong, J., & Needham, L. L. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.7534 · Cited by 1,031
In vitro molecular mechanisms of bisphenol A action.
Wetherill, Y. B., Akingbemi, B. T., Kanno, J., McLachlan, J. A., Nadal, A., Sonnenschein, C., Watson, C. S., Zoeller, R. T., & Belcher, S. M. (2007) · Reproductive Toxicology · doi:10.1016/j.reprotox.2007.05.010 · Cited by 920
Ikezuki, Y., Tsutsumi, O., Takai, Y., Kamei, Y., & Taketani, Y. (2002) · Human Reproduction · doi:10.1093/humrep/17.11.2839 · Cited by 886
Metadata
- Authors
- Nagel, S. C., vom Saal, F. S., Thayer, K. A., Dhar, M. G., Boechler, M., & Welshons, W. V.
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 1997-01
- Volume
- 105
- Issue
- 1
- Pages
- 70-76
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- OpenAlex
- W2022373675
- Cited by
- 793
- References
- 0
- FWCI
- 48.68
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol. https://app.cochat.ai/papers/10.1289/ehp.9710570
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- Nagel, S. C., vom Saal, F. S., Thayer, K. A., Dhar, M. G., Boechler, M., & Welshons, W. V. (1997). 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. https://doi.org/10.1289/ehp.9710570
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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