The promoter of the human sodium/iodide symporter responds to certain phthalate plasticisers

The diesters of benzene-1,2-dicarboxylic (phthalic) acid, the phthalates, are used to make plastics flexible and can comprise 40% of the weight of plastic. Human exposure to phthalates can occur via ingestion, inhalation and dermal routes, as well as through parenteral exposure from medical devices containing phthalates. Since earlier morphological studies showed that some phthalates induced thyroid hyperactivity, we thought it important to investigate possible effects of six major phthalates on the transcriptional activity of sodium/iodide symporter (NIS). Di-isodecyl phthalate (DIDP), benzyl butyl phthalate (BBP) and di-octyl phthalate (DOP) increased the activity of the human NIS promoter construct 2.5-, 2.6- and 2.4-fold, respectively. Likewise, these phthalates also enhanced the rat NIS endogenous mRNA expression ca. 2-fold. No effect was observed for bis-(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DINP), whereas dibutyl phthalate (DBP) appeared to down-regulate hNIS promoter. Although the demonstrated stimulation of NIS gene transcription by DIDP, BBP and DOP is not very strong, this finding is of great importance as humans are routinely exposed for long periods to phthalate plasticisers, the accumulation of which may contribute to thyroid hyperfunction.