Di-2-ethylhexylphthalate promotes thyroid cell proliferation and DNA damage through activating thyrotropin-receptor-mediated pathways in vitro and in vivo.

Di-2-ethylhexylphthalate promotes thyroid cell proliferation and DNA damage through activating thyrotropin-receptor-mediated pathways in vitro and in vivo. Food Chem Toxicol. 2018 Dec 10;: Authors: Kim S, Park GY, Yoo YJ, Jeong JS, Nam KT, Jee SH, Lim KM, Lee YS Abstract Phthalates are being suggested to be associated with altered thyroid function and proliferative changes, but detailed mechanisms remain unclear. Here, we examined the effects of di-(2-ethylhexyl) phthalate (DEHP) on DNA damage and proliferation in thyroid using thyroid carcinoma cell line, 8505C, in vitro and the rats orally treated with DEHP at 0, 0.3, 3, 30 and 150 mg/kg for 90 days from post-natal day 9 in vivo. Exposure to DHEP (1-50 μM) induced cellular proliferation, as evidenced by increased cell viability and DNA synthesis. Activation of γH2AX, a sensitive biomarker for DNA damage was observed following the exposure to DHEP (from 5 to 50 μM) with increased comet tail moment (5-100 μM) in comet assay, reflecting that DNA damage also occurred. When upstream signaling was examined, both thyrotropin receptor (TSHR)-ERK1/2 axis and TSHR-AKT axis were activated with upregulation of Pax8, a master transcriptional factor for thyroid differentiation and proliferation. Thyroid tissue from juvenile rats orally exposed to DEHP also confirmed DNA damage responses and the activation of TSHR signaling, which was evident from 0.3 to 3 mg/kg respectively. Notabl...
Source: Food and Chemical Toxicology - Category: Food Science Authors: Tags: Food Chem Toxicol Source Type: research