title: The effect of plasticisers on "sulphate supply" enzymes.
abstract: Sulphation is important in xenobiotic detoxification and in steroid and thyroid hormones synthesis, transport and metabolism. Potential endocrine disrupting actions of plasticisers were assessed by studying effects on cell viability, cell proliferation and expression of enzymes (cysteine dioxygenase, sulphite oxidase, PAPS synthase I and II) involved in the synthesis of the cofactor, PAPS, for steroid sulphotransferases. TE 671 cells were used to study the effects of exposure to alkylphenols and alkylphenolethoxylates, bisphenol A, bisphenol A methacrylate, alkyladipates, dialkyl phthalates and resorcinol. The lactate dehydrogenase assay and CellTiter 96) AQ(ueous) One Solution Cell Proliferation Assay were used to measure cytotoxicity and cell proliferation, respectively. Steady-state mRNA was assessed by semi-quantitative RT-PCR and real time RT-PCR. None of the compounds tested was cytotoxic in TE 671 cells, however, cell proliferation was significantly increased with 0.005-0.5 microM dioctyl phthalate, diisodecyl phthalate (DIP) and butylbenzyl phthalate (P<0.05, n = 4). Real time RT-PCR showed dose-dependent decreases in steady-state mRNA levels of all the enzymes studied (P<0.05, n = 4) with 0.005-0.5 microM octylphenol, bis (2-ethylhexyl) phthalate and DIP treatment. Endocrine disrupting effects of some plasticisers may be a consequence of modulation of expression of enzymes supplying PAPS for hormone sulphation.
authors.affiliation: School of Biosciences, University of Birmingham, UK.
authors.forename: N
authors.initials: N
authors.lastname: Turan
authors.forename: R H
authors.initials: RH
authors.lastname: Waring
authors.forename: D B
authors.initials: DB
authors.lastname: Ramsden
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D050558:Cysteine Dioxygenase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D052244:Endocrine Disruptors / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D010724:Phosphoadenosine Phosphosulfate / Q000096:biosynthesis*; D010968:Plasticizers / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013430:Sulfate Adenylyltransferase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D050876:Sulfite Oxidase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D009097:Multienzyme Complexes; D010636:Phenols; D010968:Plasticizers; D012333:RNA, Messenger; D010724:Phosphoadenosine Phosphosulfate; D050558:Cysteine Dioxygenase; D050876:Sulfite Oxidase; C022322:PAPS synthetase; D013430:Sulfate Adenylyltransferase