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 sulfoconjugation 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 microM (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 microM (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.
Division of Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
M
M
Shimizu
K
K
Ohta
Y
Y
Matsumoto
M
M
Fukuoka
Y
Y
Ohno
S
S
Ozawa
D015239:Arylsulfotransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D001559:Benzhydryl Compounds; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000493:pharmacokinetics* / Q000633:toxicity*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008658:Inactivation, Metabolic; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D010636:Phenols / Q000493:pharmacokinetics* / Q000633:toxicity*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013431:Sulfates / Q000633:toxicity; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D000098826:Bisphenol A Compounds
D015239:Arylsulfotransferase; D001559:Benzhydryl Compounds; D003687:Dehydroepiandrosterone; D004791:Enzyme Inhibitors; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D011506:Proteins; D012333:RNA, Messenger; D013431:Sulfates; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; C051838:TFF1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds