title: A role for sulfation-desulfation in the uptake of bisphenol a into breast tumor cells.
abstract: Bisphenol A (BPA) is a widely used plasticizer whose estrogenic properties may impact hormone-responsive disorders and fetal development. In vivo, BPA appears to have greater activity than is suggested by its estrogen receptor (ER) binding affinity. This may be a result of BPA sulfation/desulfation providing a pathway for selective uptake into hormone-responsive cells. BPA is a substrate for estrogen sulfotransferase, and bisphenol A sulfate (BPAS) and disulfate are substrates for estrone sulfatase. Although the sulfated xenobiotics bind poorly to the ER, both stimulated the growth of receptor-positive breast tumor cells. Treatment of MCF-7 cells with BPAS leads to desulfation and uptake of BPA. No BPAS is found inside the cells. These findings suggest a mechanism for the selective uptake of BPA into cells expressing estrone sulfatase. Therefore, sulfation may increase the estrogenic potential of xenobiotics.
authors.affiliation: Department of Chemistry, Indiana University, 800 East Kirkwood Avenue, Bloomington, IN 47405, USA.
authors.forename: Cheri L
authors.initials: CL
authors.lastname: Stowell
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Barvian
authors.forename: Peter C M
authors.initials: PC
authors.lastname: Young
authors.forename: Robert M
authors.initials: RM
authors.lastname: Bigsby
authors.forename: Dawn E
authors.initials: DE
authors.lastname: Verdugo
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Bertozzi
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Widlanski
mesh_terms: D001559:Benzhydryl Compounds; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism*; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D012680:Sensitivity and Specificity; D015238:Sulfotransferases / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013461:Sulfur Oxides / Q000737:chemistry*; D013463:Sulfuric Acid Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D010636:Phenols; D011960:Receptors, Estrogen; D015238:Sulfotransferases; D013461:Sulfur Oxides; D013463:Sulfuric Acid Esters; C574799:bisphenol A disulfate; D000098826:Bisphenol A Compounds; C020122:estrone sulfotransferase; C011118:sulfur trioxide; C006780:bisphenol A