The effect of plasticisers on 'sulphate supply' enzymes

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 CeIlTiter 96 (R) 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 mu M 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 mu M octylphenol, his (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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.