Sulfation of bisphenol A abolished its estrogenicity based on proliferation and gene expression in human breast cancer MCF-7 cells

Bisphenol A, an endocrine-disrupting chemical, is widely used in many consumer products. We previously showed the sulfo-conjugation of bisphenol A catalyzed by a human thermostable phenol sulfotransferase, ST1A3. The estrogenic potency of bisphenol A sulfate was compared with that of bisphenol A by an E-screen assay using human breast cancer MCF-7 cells. An increase in the expression level of an estrogen-responsive pS2 gene was also examined using MCF-7 cells after exposure to bisphenol A and its sulfate for their estrogenicity. Bisphenol A sulfate did not exhibit estrogenic effects at 0.1 muM (E-screen assay) and 1 mM (pS2 gene expression) compared with bisphenol A, which exhibited the effects at 3 nm (E-screen assay) and 1 muM (pS2 gene expression), respectively. We have therefore evaluated major roles of cytosolic phenol sulfotransferase in the human liver. Bisphenol A sulfation in human liver cytosols was inhibited by more than 90% by p-nitrophenol and quercetin, a typical substrate and specific inhibitor of phenol sulfotransferase, respectively. These results indicated that the estrogenicity of bisphenol A was abolished through its sulfation catalyzed by a human hepatic thermostable phenol sulfotransferase. (C) 2002 Elsevier Science Ltd. All rights reserved.